Variant 1-15328410-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001391957.1(FHAD1):c.1691C>T(p.Thr564Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,528,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

FHAD1
NM_001391957.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0760

Variant links:

Genes affected

FHAD1 (HGNC:29408): (forkhead associated phosphopeptide binding domain 1)

FHAD1 links:

FHAD1-AS1 (HGNC:41241): (FHAD1 antisense RNA 1)

FHAD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.00945574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHAD1	NM_001391957.1 linkuse as main transcript	c.1691C>T	p.Thr564Met	missense_variant	13/34	ENST00000688493.1	NP_001378886.1
FHAD1-AS1	NR_148919.1 linkuse as main transcript	n.1379G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHAD1	ENST00000688493.1 linkuse as main transcript	c.1691C>T	p.Thr564Met	missense_variant	13/34		NM_001391957.1	ENSP00000509124	P2
FHAD1-AS1	ENST00000428747.1 linkuse as main transcript	n.1375G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000304

AC:

AN:

137970

Hom.:

AF XY:

0.000352

AC XY:

AN XY:

73954

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000131

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00181

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000129

AC:

177

AN:

1376092

Hom.:

Cov.:

AF XY:

0.000159

AC XY:

108

AN XY:

679260

show subpopulations

Gnomad4 AFR exome

AF:

0.0000671

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000608

Gnomad4 OTH exome

AF:

0.000141

GnomAD4 genome

AF:

0.0000855

AC:

AN:

151964

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.000370

AC:

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.1691C>T (p.T564M) alteration is located in exon 13 (coding exon 12) of the FHAD1 gene. This alteration results from a C to T substitution at nucleotide position 1691, causing the threonine (T) at amino acid position 564 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.8

DANN

Benign

0.88

DEOGEN2

Benign

0.0045

T;T;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.77

T;.;T;T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.0095

T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.0

L;L;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

N;N;N;.;D

REVEL

Benign

0.17

Sift

Benign

0.094

T;T;T;.;D

Sift4G

Benign

0.15

T;T;T;D;T

Polyphen

0.14

B;B;.;.;.

Vest4

0.11

MutPred

0.12

Loss of phosphorylation at T564 (P = 0.1511);Loss of phosphorylation at T564 (P = 0.1511);.;.;.;

MVP

0.048

ClinPred

0.014

GERP RS

-2.7

Varity_R

0.015

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over