dbSNP rs894258808: FAM43A:p.Arg285His (chr3-194687680-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_153690.5(FAM43A):c.854G>A(p.Arg285His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,410,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R285L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FAM43A
NM_153690.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

FAM43A (HGNC:26888): (family with sequence similarity 43 member A)

FAM43A 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=0.046738982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM43A	NM_153690.5 link	c.854G>A	p.Arg285His	missense_variant	Exon 1 of 1	ENST00000329759.6	NP_710157.2	Q8N2R8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM43A	ENST00000329759.6 link	c.854G>A	p.Arg285His	missense_variant	Exon 1 of 1	6	NM_153690.5	ENSP00000371397.1		Q8N2R8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

166018

Hom.:

AF XY:

0.0000113

AC XY:

AN XY:

88320

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:

0.0000309

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1410776

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697022

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:

0.00000276

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.6

DANN

Benign

0.94

DEOGEN2

Benign

0.015

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.52

M_CAP

Benign

0.036

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.80

REVEL

Benign

0.16

Sift

Benign

0.17

Sift4G

Benign

0.31

Polyphen

0.0030

Vest4

0.067

MutPred

0.21

Gain of loop (P = 0.0851);

MVP

0.24

ClinPred

0.025

GERP RS

-3.0

Varity_R

0.028

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over