10-47999735-C-T

Variant names:

• chr10-47999735-C-T
• rs1423095681
• NM_001137548.3:c.31G>A

Variant summary

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

The NM_001137548.3(FAM25C):​c.31G>A​(p.Glu11Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000067 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM25C NM_001137548.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.507

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09565878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM25C	NM_001137548.3	c.31G>A	p.Glu11Lys	missense_variant	Exon 1 of 3	ENST00000617224.3	NP_001131020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM25C	ENST00000617224.3	c.31G>A	p.Glu11Lys	missense_variant	Exon 1 of 3	1	NM_001137548.3	ENSP00000485370.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10 AN: 149108 Hom.: 0 Cov.: 20 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000666

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000120

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000121 AC: 167 AN: 1385148 Hom.: 0 Cov.: 31 AF XY: 0.000124 AC XY: 85 AN XY: 683716

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000145

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000532

Gnomad4 SAS exome AF: 0.0000381

Gnomad4 FIN exome AF: 0.000104

Gnomad4 NFE exome AF: 0.000119

Gnomad4 OTH exome AF: 0.000139

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000671 AC: 10 AN: 149108 Hom.: 0 Cov.: 20 AF XY: 0.0000551 AC XY: 4 AN XY: 72630

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000666

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000220

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000120

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000270 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.31G>A (p.E11K) 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 31, causing the glutamic acid (E) at amino acid position 11 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	-0.41	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Benign	0.78
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0098	N
M_CAP	Benign	0.00049	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.60	T
Sift4G	Pathogenic	0.0	D
Vest4		0.30
MVP		0.030
ClinPred		0.12	T
GERP RS		-1.1
Varity_R		0.11
gMVP		0.13

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

Other links and lift over

dbSNP: rs1423095681; hg19: chr10-49207769;