rs1555256635

Variant names:

• chr10-47997700-T-C
• rs1555256635
• NM_001137548.3:c.113A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001137548.3(FAM25C):​c.113A>G​(p.His38Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 27)
  • Exomes 𝑓: 0.0000058 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM25C NM_001137548.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

Genes affected

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

ENSG00000304615 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14901379).

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.113A>G	p.His38Arg	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.113A>G	p.His38Arg	missense	Exon 2 of 3	ENSP00000485370.1	B3EWG5
	ENSG00000304615	ENST00000804955.1		n.175-12444T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD2 exomes AF: 0.0000166 AC: 1 AN: 60184 AF XY: 0.0000332

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000585 AC: 8 AN: 1368016 Hom.: 0 Cov.: 29 AF XY: 0.00000740 AC XY: 5 AN XY: 675990

African (AFR) AF: 0.00 AC: 0 AN: 31258

American (AMR) AF: 0.00 AC: 0 AN: 35644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24994

East Asian (EAS) AF: 0.00 AC: 0 AN: 35688

South Asian (SAS) AF: 0.0000763 AC: 6 AN: 78672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42372

Middle Eastern (MID) AF: 0.000249 AC: 1 AN: 4012

European-Non Finnish (NFE) AF: 9.45e-7 AC: 1 AN: 1058318

Other (OTH) AF: 0.00 AC: 0 AN: 57058

GnomAD4 genome Cov.: 27

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.66
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.043	N
M_CAP	Benign	0.00063	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.4
PrimateAI	Uncertain	0.53	T
Sift4G	Uncertain	0.034	D
Vest4		0.28
MVP		0.055
ClinPred		0.097	T
GERP RS		0.34
Varity_R		0.12
gMVP		0.26
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1555256635; hg19: chr10-49205734;