10-47999737-G-A

Variant names:

• chr10-47999737-G-A
• rs1842852339
• NM_001137548.3:c.29C>T

Variant summary

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

The NM_001137548.3(FAM25C):​c.29C>T​(p.Ala10Val) 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: not found (cov: 20)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM25C NM_001137548.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

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=0.09954116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM25C	NM_001137548.3	c.29C>T	p.Ala10Val	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.29C>T	p.Ala10Val	missense_variant	Exon 1 of 3	1	NM_001137548.3	ENSP00000485370.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.23e-7 AC: 1 AN: 1383410 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 682940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

Alfa AF: 0.0000936 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.29C>T (p.A10V) alteration is located in exon 1 (coding exon 1) of the FAM25C gene. This alteration results from a C to T substitution at nucleotide position 29, causing the alanine (A) at amino acid position 10 to be replaced by a valine (V). 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	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.027	N
M_CAP	Benign	0.00062	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.51	T
Sift4G	Pathogenic	0.0	D
Vest4		0.33
MVP		0.030
ClinPred		0.21	T
GERP RS		-0.75
Varity_R		0.072
gMVP		0.21

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: rs1842852339; hg19: chr10-49207771;