Variant chr1-15289481-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001391957.1(FHAD1):c.383C>A(p.Pro128His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,399,522 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

FHAD1
NM_001391957.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.214

Variant links:

Genes affected

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

FHAD1 links:

LOC124903853 (HGNC:):

LOC124903853 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17469653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHAD1	NM_001391957.1 linkuse as main transcript	c.383C>A	p.Pro128His	missense_variant	4/34	ENST00000688493.1	NP_001378886.1
LOC124903853	XR_007065482.1 linkuse as main transcript	n.552G>T		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.383C>A	p.Pro128His	missense_variant	4/34		NM_001391957.1	ENSP00000509124	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000638

AC:

AN:

156700

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

82992

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000429

AC:

AN:

1399522

Hom.:

Cov.:

AF XY:

0.00000579

AC XY:

AN XY:

690266

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:

0.00000556

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.00000378

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

Aug 09, 2021

The c.383C>A (p.P128H) alteration is located in exon 4 (coding exon 3) of the FHAD1 gene. This alteration results from a C to A substitution at nucleotide position 383, causing the proline (P) at amino acid position 128 to be replaced by a histidine (H). 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

0.090

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0017

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.38

T;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.059

Sift

Benign

0.058

T;T

Sift4G

Uncertain

0.019

D;D

Polyphen

0.98

D;D

Vest4

0.26

MutPred

0.18

Loss of glycosylation at P128 (P = 0.0172);Loss of glycosylation at P128 (P = 0.0172);

MVP

0.088

ClinPred

0.18

GERP RS

2.0

Varity_R

0.066

gMVP

0.26

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