chr1-27547384-C-T

Variant names:

• chr1-27547384-C-T
• rs141730488
• NM_001371928.1:c.4732G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001371928.1(AHDC1):​c.4732G>A​(p.Gly1578Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,558,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: AHDC1 NM_001371928.1 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.97
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.057837635).
• BS2: High AC in GnomAd4 at 11 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.4732G>A	p.Gly1578Ser	missense	Exon 8 of 9	NP_001358857.1	Q5TGY3
	AHDC1	NM_001029882.3		c.4732G>A	p.Gly1578Ser	missense	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.4732G>A	p.Gly1578Ser	missense	Exon 8 of 9	ENSP00000501218.1	Q5TGY3
	AHDC1	ENST00000247087.10	TSL:5	c.4732G>A	p.Gly1578Ser	missense	Exon 5 of 6	ENSP00000247087.4	Q5TGY3
	AHDC1	ENST00000374011.6	TSL:5	c.4732G>A	p.Gly1578Ser	missense	Exon 6 of 7	ENSP00000363123.2	Q5TGY3

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000342 AC: 7 AN: 204518 AF XY: 0.0000273

Gnomad AFR exome AF: 0.000330

Gnomad AMR exome AF: 0.0000763

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000640 AC: 9 AN: 1406028 Hom.: 0 Cov.: 30 AF XY: 0.0000115 AC XY: 8 AN XY: 694530

African (AFR) AF: 0.000127 AC: 4 AN: 31572

American (AMR) AF: 0.0000557 AC: 2 AN: 35908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22280

East Asian (EAS) AF: 0.00 AC: 0 AN: 39242

South Asian (SAS) AF: 0.0000383 AC: 3 AN: 78366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084882

Other (OTH) AF: 0.00 AC: 0 AN: 57860

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152360 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74506

African (AFR) AF: 0.000265 AC: 11 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000163 Hom.: 0

Bravo AF: 0.0000567

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.070
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.16
Sift	Benign	0.19	T
Sift4G	Benign	1.0	T
Polyphen		0.79	P
Vest4		0.23
MVP		0.86
MPC		1.5
ClinPred		0.055	T
GERP RS		5.3
Varity_R		0.061
gMVP		0.21
Mutation Taster		=86/14	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: rs141730488; hg19: chr1-27873895; COSMIC: COSV107208492; COSMIC: COSV107208492;