dbSNP rs377599440: FAM131C:p.His135Arg (chr1-16059916-T-C) – 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_182623.3(FAM131C):c.404A>G(p.His135Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,363,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 19)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

FAM131C
NM_182623.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0160

Publications

0 publications found

Variant links:

Genes affected

FAM131C (HGNC:26717): (family with sequence similarity 131 member C)

FAM131C 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=0.038629085).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182623.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131C	NM_182623.3	MANE Select	c.404A>G	p.His135Arg	missense	Exon 5 of 7	NP_872429.2	Q96AQ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM131C	ENST00000375662.5	TSL:1 MANE Select	c.404A>G	p.His135Arg	missense	Exon 5 of 7	ENSP00000364814.4	Q96AQ9
FAM131C	ENST00000943020.1		c.368A>G	p.His123Arg	missense	Exon 4 of 6	ENSP00000613079.1
FAM131C	ENST00000904375.1		c.269-312A>G		intron	N/A	ENSP00000574434.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000809

AC:

AN:

247218

AF XY:

0.0000148

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1363348

Hom.:

Cov.:

AF XY:

0.0000133

AC XY:

AN XY:

676998

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32250

American (AMR)

AF:

0.00

AC:

AN:

39058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23270

East Asian (EAS)

AF:

0.00

AC:

AN:

27318

South Asian (SAS)

AF:

0.00

AC:

AN:

78756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4096

European-Non Finnish (NFE)

AF:

0.0000133

AC:

AN:

1055666

Other (OTH)

AF:

0.00

AC:

AN:

54668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.0000312

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

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

0.073

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.0

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0038

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.42

M_CAP

Benign

0.0060

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

PhyloP100

-0.016

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

REVEL

Benign

0.026

Sift

Benign

0.24

Sift4G

Benign

0.57

Polyphen

0.0030

Vest4

0.11

MVP

0.20

MPC

0.54

ClinPred

0.068

GERP RS

2.2

Varity_R

0.056

gMVP

0.32

Mutation Taster

=87/13

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