NM_001371928.1:c.1411G>A

Variant names:

• chr1-27550705-C-T
• rs147276945
• NM_001371928.1:c.1411G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001371928.1(AHDC1):​c.1411G>A​(p.Val471Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00845 in 1,608,408 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0087 (80 hom.)
• Consequence: AHDC1 NM_001371928.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.44
• Publications: 7 publications found

Genes affected

AHDC1 (HGNC:25230): (AT-hook DNA binding motif containing 1) This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome. [provided by RefSeq, Jun 2014]

AHDC1 Gene-Disease associations (from GenCC):

• AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Orphanet, G2P, ClinGen

ENSG00000300470 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00791198).
• BP6: Variant 1-27550705-C-T is Benign according to our data. Variant chr1-27550705-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00612 (933/152392) while in subpopulation NFE AF = 0.0104 (706/68044). AF 95% confidence interval is 0.00974. There are 2 homozygotes in GnomAd4. There are 439 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 933 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371928.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHDC1	NM_001371928.1	MANE Select	c.1411G>A	p.Val471Met	missense	Exon 8 of 9	NP_001358857.1
	AHDC1	NM_001029882.3		c.1411G>A	p.Val471Met	missense	Exon 6 of 7	NP_001025053.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHDC1	ENST00000673934.1	MANE Select	c.1411G>A	p.Val471Met	missense	Exon 8 of 9	ENSP00000501218.1
	AHDC1	ENST00000247087.10	TSL:5	c.1411G>A	p.Val471Met	missense	Exon 5 of 6	ENSP00000247087.4
	AHDC1	ENST00000374011.6	TSL:5	c.1411G>A	p.Val471Met	missense	Exon 6 of 7	ENSP00000363123.2

Frequencies

GnomAD3 genomes AF: 0.00613 AC: 933 AN: 152274 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00580 AC: 1374 AN: 236774 AF XY: 0.00582

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.0183

Gnomad EAS exome AF: 0.0000576

Gnomad FIN exome AF: 0.00294

Gnomad NFE exome AF: 0.00966

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00870 AC: 12665 AN: 1456016 Hom.: 80 Cov.: 60 AF XY: 0.00846 AC XY: 6128 AN XY: 724006

African (AFR) AF: 0.00129 AC: 43 AN: 33354

American (AMR) AF: 0.00166 AC: 73 AN: 43964

Ashkenazi Jewish (ASJ) AF: 0.0195 AC: 507 AN: 26004

East Asian (EAS) AF: 0.000559 AC: 22 AN: 39372

South Asian (SAS) AF: 0.000257 AC: 22 AN: 85470

European-Finnish (FIN) AF: 0.00335 AC: 175 AN: 52236

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5766

European-Non Finnish (NFE) AF: 0.0103 AC: 11430 AN: 1109682

Other (OTH) AF: 0.00642 AC: 386 AN: 60168

GnomAD4 genome AF: 0.00612 AC: 933 AN: 152392 Hom.: 2 Cov.: 33 AF XY: 0.00589 AC XY: 439 AN XY: 74522

African (AFR) AF: 0.00231 AC: 96 AN: 41600

American (AMR) AF: 0.00202 AC: 31 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00216 AC: 23 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0104 AC: 706 AN: 68044

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00797 Hom.: 11

Bravo AF: 0.00572

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.0135 AC: 52

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.0113 AC: 97

ExAC AF: 0.00544 AC: 660

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Jul 18, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AHDC1: PP2, BS1, BS2

Dec 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AHDC1-related disorder Benign:1

Mar 17, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.44
MVP		0.20
MPC		1.4
ClinPred		0.0098	T
GERP RS		4.4
Varity_R		0.11
gMVP		0.75
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147276945; hg19: chr1-27877216; COSMIC: COSV55940449; COSMIC: COSV55940449;