Genetic Variant FHAD1:p.Arg624Gln (chr1-15329506-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001391957.1(FHAD1):c.1871G>A(p.Arg624Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,398,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000018 ( 0 hom. )

Consequence

FHAD1
NM_001391957.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.532

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04150188).

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.1871G>A	p.Arg624Gln	missense	Exon 14 of 34	NP_001378886.1	A0A804HIA4
FHAD1	NM_052929.2		c.1871G>A	p.Arg624Gln	missense	Exon 14 of 31	NP_443161.1	B1AJZ9-1
FHAD1-AS1	NR_148918.1		n.286C>T		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.1871G>A	p.Arg624Gln	missense	Exon 14 of 34	ENSP00000509124.1	A0A804HIA4
FHAD1	ENST00000471347.5	TSL:1	n.337G>A		non_coding_transcript_exon	Exon 3 of 24
FHAD1	ENST00000683790.1		c.1871G>A	p.Arg624Gln	missense	Exon 14 of 34	ENSP00000506973.1	A0A804HIA4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000384

AC:

AN:

156136

AF XY:

0.0000121

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000184

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000499

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1398552

Hom.:

Cov.:

AF XY:

0.0000159

AC XY:

AN XY:

689780

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31596

American (AMR)

AF:

0.00

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.000140

AC:

AN:

35734

South Asian (SAS)

AF:

0.0000252

AC:

AN:

79230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0000139

AC:

AN:

1078800

Other (OTH)

AF:

0.0000517

AC:

AN:

58004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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.:

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000393

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

0.079

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.39

CADD

Benign

4.4

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.31

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.4

PhyloP100

-0.53

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.50

REVEL

Benign

0.16

Sift

Benign

0.54

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.096

MVP

0.055

ClinPred

0.033

GERP RS

-2.3

Varity_R

0.022

gMVP

0.054

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

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