Genetic Variant FHAD1:p.Arg511Trp (chr1-15327116-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001391957.1(FHAD1):c.1531C>T(p.Arg511Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,399,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000093 ( 0 hom. )

Consequence

FHAD1
NM_001391957.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

Publications

1 publications found

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:

EFHD2-AS1 (HGNC:55801): (EFHD2 antisense RNA 1)

EFHD2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20314535).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391957.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FHAD1	NM_001391957.1	MANE Select	c.1531C>T	p.Arg511Trp	missense	Exon 12 of 34	NP_001378886.1	A0A804HIA4
FHAD1	NM_052929.2		c.1531C>T	p.Arg511Trp	missense	Exon 12 of 31	NP_443161.1	B1AJZ9-1
FHAD1-AS1	NR_148918.1		n.2676G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FHAD1	ENST00000688493.1	MANE Select	c.1531C>T	p.Arg511Trp	missense	Exon 12 of 34	ENSP00000509124.1	A0A804HIA4
FHAD1	ENST00000683790.1		c.1531C>T	p.Arg511Trp	missense	Exon 12 of 34	ENSP00000506973.1	A0A804HIA4
FHAD1	ENST00000968213.1		c.1531C>T	p.Arg511Trp	missense	Exon 12 of 32	ENSP00000638272.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000129

AC:

AN:

155588

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000407

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:

0.00000929

AC:

AN:

1399072

Hom.:

Cov.:

AF XY:

0.00000725

AC XY:

AN XY:

690044

show subpopulations

African (AFR)

AF:

0.0000633

AC:

AN:

31596

American (AMR)

AF:

0.0000280

AC:

AN:

35676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35730

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49182

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000371

AC:

AN:

1078824

Other (OTH)

AF:

0.0000690

AC:

AN:

58000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0049

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.46

MutationAssessor

Benign

0.55

PhyloP100

1.8

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.4

REVEL

Benign

0.27

Sift

Benign

0.030

Sift4G

Uncertain

0.016

Polyphen

0.91

Vest4

0.12

MutPred

0.37

Loss of disorder (P = 0.0079)

MVP

0.32

ClinPred

0.69

GERP RS

5.4

Varity_R

0.087

gMVP

0.087

Mutation Taster

=82/18

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over