NM_001371928.1:c.4782C>T

Variant names:

• chr1-27547334-G-A
• rs61742782
• NM_001371928.1:c.4782C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001371928.1(AHDC1):​c.4782C>T​(p.Pro1594Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,552,134 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (42 hom.)
• Consequence: AHDC1 NM_001371928.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.43
• Publications: 3 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: Illumina, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000300470 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-27547334-G-A is Benign according to our data. Variant chr1-27547334-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 783928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.42 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00404 (615/152328) while in subpopulation NFE AF = 0.00657 (447/68036). AF 95% confidence interval is 0.00607. There are 3 homozygotes in GnomAd4. There are 269 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 615 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHDC1	NM_001371928.1	MANE Select	c.4782C>T	p.Pro1594Pro	synonymous	Exon 8 of 9	NP_001358857.1	Q5TGY3
	AHDC1	NM_001029882.3		c.4782C>T	p.Pro1594Pro	synonymous	Exon 6 of 7	NP_001025053.1	Q5TGY3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHDC1	ENST00000673934.1	MANE Select	c.4782C>T	p.Pro1594Pro	synonymous	Exon 8 of 9	ENSP00000501218.1	Q5TGY3
	AHDC1	ENST00000247087.10	TSL:5	c.4782C>T	p.Pro1594Pro	synonymous	Exon 5 of 6	ENSP00000247087.4	Q5TGY3
	AHDC1	ENST00000374011.6	TSL:5	c.4782C>T	p.Pro1594Pro	synonymous	Exon 6 of 7	ENSP00000363123.2	Q5TGY3

Frequencies

GnomAD3 genomes AF: 0.00401 AC: 611 AN: 152210 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.00392 AC: 778 AN: 198486 AF XY: 0.00381

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.00295

Gnomad ASJ exome AF: 0.0144

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000164

Gnomad NFE exome AF: 0.00539

Gnomad OTH exome AF: 0.00304

GnomAD4 exome AF: 0.00621 AC: 8695 AN: 1399806 Hom.: 42 Cov.: 30 AF XY: 0.00608 AC XY: 4203 AN XY: 691522

African (AFR) AF: 0.00112 AC: 35 AN: 31146

American (AMR) AF: 0.00265 AC: 89 AN: 33616

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 327 AN: 21748

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39274

South Asian (SAS) AF: 0.00565 AC: 432 AN: 76406

European-Finnish (FIN) AF: 0.000438 AC: 22 AN: 50246

Middle Eastern (MID) AF: 0.00386 AC: 21 AN: 5444

European-Non Finnish (NFE) AF: 0.00682 AC: 7390 AN: 1084318

Other (OTH) AF: 0.00656 AC: 378 AN: 57608

GnomAD4 genome AF: 0.00404 AC: 615 AN: 152328 Hom.: 3 Cov.: 33 AF XY: 0.00361 AC XY: 269 AN XY: 74492

African (AFR) AF: 0.00103 AC: 43 AN: 41568

American (AMR) AF: 0.00281 AC: 43 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00657 AC: 447 AN: 68036

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00465 Hom.: 2

Bravo AF: 0.00404

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.5
DANN	Benign	0.90
PhyloP100		-1.4
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs61742782; hg19: chr1-27873845; COSMIC: COSV55937478; COSMIC: COSV55937478;