Variant 10-47999714-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001137548.3(FAM25C):c.52G>A(p.Glu18Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000060 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM25C
NM_001137548.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

Variant links:

Genes affected

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

FAM25C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12069708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM25C	NM_001137548.3 linkuse as main transcript	c.52G>A	p.Glu18Lys	missense_variant	1/3	ENST00000617224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM25C	ENST00000617224.3 linkuse as main transcript	c.52G>A	p.Glu18Lys	missense_variant	1/3	1	NM_001137548.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150444

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000579

AC:

AN:

69036

Hom.:

AF XY:

0.0000290

AC XY:

AN XY:

34490

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:

0.000156

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000596

AC:

AN:

1391774

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

686572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000725

Gnomad4 OTH exome

AF:

0.0000521

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000664

AC:

AN:

150562

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73470

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2023

The c.52G>A (p.E18K) alteration is located in exon 1 (coding exon 1) of the FAM25C gene. This alteration results from a G to A substitution at nucleotide position 52, causing the glutamic acid (E) at amino acid position 18 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.045

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.031

M_CAP

Benign

0.00066

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

Sift4G

Pathogenic

0.0

Vest4

0.24

MVP

0.048

ClinPred

0.20

GERP RS

0.57

Varity_R

0.11

gMVP

0.40

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over