Genetic Variant AHDC1:p.Thr34Ser (chr1-27552016-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001371928.1(AHDC1):c.100A>T(p.Thr34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T34P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AHDC1
NM_001371928.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

Publications

0 publications found

Variant links:

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

AHDC1 links:

ENSG00000300470 (HGNC:):

ENSG00000300470 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059786826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHDC1	NM_001371928.1 link	c.100A>T	p.Thr34Ser	missense_variant	Exon 8 of 9	ENST00000673934.1	NP_001358857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHDC1	ENST00000673934.1 link	c.100A>T	p.Thr34Ser	missense_variant	Exon 8 of 9		NM_001371928.1	ENSP00000501218.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

21662

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

53166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

25834

African (AFR)

AF:

0.00

AC:

AN:

1216

American (AMR)

AF:

0.00

AC:

AN:

1082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

690

East Asian (EAS)

AF:

0.00

AC:

AN:

812

South Asian (SAS)

AF:

0.00

AC:

AN:

2988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

41896

Other (OTH)

AF:

0.00

AC:

AN:

2068

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

21662

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

10062

African (AFR)

AF:

0.00

AC:

AN:

5730

American (AMR)

AF:

0.00

AC:

AN:

2018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

586

East Asian (EAS)

AF:

0.00

AC:

AN:

522

South Asian (SAS)

AF:

0.00

AC:

AN:

528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

10710

Other (OTH)

AF:

0.00

AC:

AN:

238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.011

T;T;T;T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.37

.;.;T;.;.

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.060

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N;N;N

PhyloP100

2.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.31

N;.;N;.;.

REVEL

Benign

0.061

Sift

Benign

0.15

T;.;T;.;.

Sift4G

Benign

0.81

T;.;T;.;.

Polyphen

0.0

B;B;B;B;B

Vest4

0.14

MutPred

0.16

Loss of catalytic residue at T34 (P = 0.1069);Loss of catalytic residue at T34 (P = 0.1069);Loss of catalytic residue at T34 (P = 0.1069);Loss of catalytic residue at T34 (P = 0.1069);Loss of catalytic residue at T34 (P = 0.1069);

MVP

0.11

MPC

0.96

ClinPred

0.17

GERP RS

0.51

Varity_R

0.068

gMVP

0.075

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over