dbSNP rs1271328902: FAM25C:p.Val28Met (chr10-47997731-C-T) – 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_001137548.3(FAM25C):c.82G>A(p.Val28Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 150,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 27)

Exomes 𝑓: 0.000067 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

FAM25C
NM_001137548.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

Publications

0 publications found

Variant links:

Genes affected

FAM25C (HGNC:23586): (family with sequence similarity 25 member C)

FAM25C links:

ENSG00000304615 (HGNC:):

ENSG00000304615 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=0.096984565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137548.3. 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
	FAM25C	NM_001137548.3	MANE Select	c.82G>A	p.Val28Met	missense	Exon 2 of 3	NP_001131020.1	B3EWG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM25C	ENST00000617224.3	TSL:1 MANE Select	c.82G>A	p.Val28Met	missense	Exon 2 of 3	ENSP00000485370.1	B3EWG5
	ENSG00000304615	ENST00000804955.1		n.175-12413C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000113

AC:

AN:

149956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000269

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000743

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000128

AC:

AN:

77956

AF XY:

0.0000756

show subpopulations

Gnomad AFR exome

AF:

0.000165

Gnomad AMR exome

AF:

0.0000683

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000115

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000953

Gnomad OTH exome

AF:

0.000413

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000673

AC:

AN:

1367360

Hom.:

Cov.:

AF XY:

0.0000710

AC XY:

AN XY:

675754

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

31208

American (AMR)

AF:

0.0000281

AC:

AN:

35650

Ashkenazi Jewish (ASJ)

AF:

0.0000401

AC:

AN:

24966

East Asian (EAS)

AF:

0.0000841

AC:

AN:

35668

South Asian (SAS)

AF:

0.0000254

AC:

AN:

78632

European-Finnish (FIN)

AF:

0.0000219

AC:

AN:

45734

Middle Eastern (MID)

AF:

0.000499

AC:

AN:

4008

European-Non Finnish (NFE)

AF:

0.0000654

AC:

AN:

1054574

Other (OTH)

AF:

0.000123

AC:

AN:

56920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.000113

AC:

AN:

150074

Hom.:

Cov.:

AF XY:

0.0000956

AC XY:

AN XY:

73212

show subpopulations

African (AFR)

AF:

0.000268

AC:

AN:

40998

American (AMR)

AF:

0.00

AC:

AN:

14974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3428

East Asian (EAS)

AF:

0.000196

AC:

AN:

5112

South Asian (SAS)

AF:

0.00

AC:

AN:

4620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000743

AC:

AN:

67256

Other (OTH)

AF:

0.00

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0000872

Hom.:

Bravo

AF:

0.0000793

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

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.025

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.019

M_CAP

Benign

0.00065

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.0

PhyloP100

1.4

PrimateAI

Uncertain

0.54

Sift4G

Benign

0.073

Vest4

0.25

MVP

0.055

ClinPred

0.083

GERP RS

0.34

Varity_R

0.087

gMVP

0.21

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over