Variant 1-15341792-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001391957.1(FHAD1):c.2034G>A(p.Arg678=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FHAD1
NM_001391957.1 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

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 -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21671495).

BP7

Synonymous conserved (PhyloP=1.76 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHAD1	NM_001391957.1 linkuse as main transcript	c.2034G>A	p.Arg678=	synonymous_variant	16/34	ENST00000688493.1	NP_001378886.1
FHAD1-AS1	NR_148919.1 linkuse as main transcript	n.108+1984C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHAD1	ENST00000688493.1 linkuse as main transcript	c.2034G>A	p.Arg678=	synonymous_variant	16/34		NM_001391957.1	ENSP00000509124	P2
FHAD1-AS1	ENST00000428747.1 linkuse as main transcript	n.101+1984C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000634

AC:

AN:

157642

Hom.:

AF XY:

0.00

AC XY:

AN XY:

83264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000214

AC:

AN:

1399426

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

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

Mar 11, 2022

The c.1963G>A (p.G655R) alteration is located in exon 15 (coding exon 14) of the FHAD1 gene. This alteration results from a G to A substitution at nucleotide position 1963, causing the glycine (G) at amino acid position 655 to be replaced by an arginine (R). 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

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.7

DANN

Benign

0.85

DEOGEN2

Benign

0.00082

T;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.55

T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.088

Sift

Benign

0.32

T;T

Sift4G

Benign

0.71

T;T

Polyphen

1.0

D;D

Vest4

0.16

MutPred

0.20

Gain of MoRF binding (P = 0.0042);Gain of MoRF binding (P = 0.0042);

MVP

0.11

ClinPred

0.32

GERP RS

3.6

Varity_R

0.12

gMVP

0.12

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