Genetic Variant FAM131C:p.Gln185Glu (chr1-16059503-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_182623.3(FAM131C):c.553C>G(p.Gln185Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,610,976 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

FAM131C
NM_182623.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

Publications

1 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.12232399).

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.553C>G	p.Gln185Glu	missense	Exon 6 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.553C>G	p.Gln185Glu	missense	Exon 6 of 7	ENSP00000364814.4	Q96AQ9
FAM131C	ENST00000943020.1		c.517C>G	p.Gln173Glu	missense	Exon 5 of 6	ENSP00000613079.1
FAM131C	ENST00000904375.1		c.370C>G	p.Gln124Glu	missense	Exon 5 of 6	ENSP00000574434.1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000200

AC:

AN:

245054

AF XY:

0.000225

show subpopulations

Gnomad AFR exome

AF:

0.0000659

Gnomad AMR exome

AF:

0.000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.000253

Gnomad OTH exome

AF:

0.000505

GnomAD4 exome

AF:

0.000243

AC:

355

AN:

1458898

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

165

AN XY:

725510

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33446

American (AMR)

AF:

0.000429

AC:

AN:

44336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39604

South Asian (SAS)

AF:

0.00

AC:

AN:

85804

European-Finnish (FIN)

AF:

0.000339

AC:

AN:

53034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000268

AC:

298

AN:

1110678

Other (OTH)

AF:

0.000299

AC:

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

AF:

0.000250

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41486

American (AMR)

AF:

0.000327

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4776

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

67966

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000157

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

0.087

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.025

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.74

M_CAP

Benign

0.011

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

PhyloP100

2.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.58

REVEL

Benign

0.089

Sift

Benign

0.048

Sift4G

Benign

0.38

Polyphen

0.57

Vest4

0.36

MVP

0.35

MPC

0.76

ClinPred

0.031

GERP RS

3.9

Varity_R

0.075

gMVP

0.10

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over