rs193920897

Variant names:

• chr10-59252904-A-T
• rs193920897
• NM_198215.4:c.1427T>A

Variant summary

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

The NM_198215.4(FAM13C):​c.1427T>A​(p.Leu476His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM13C NM_198215.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.35
• Publications: 0 publications found

Genes affected

FAM13C (HGNC:19371): (family with sequence similarity 13 member C)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198215.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13C	NM_198215.4	MANE Select	c.1427T>A	p.Leu476His	missense	Exon 12 of 14	NP_937858.2
	FAM13C	NM_001347852.2		c.1427T>A	p.Leu476His	missense	Exon 12 of 13	NP_001334781.1
	FAM13C	NM_001347849.2		c.1424T>A	p.Leu475His	missense	Exon 12 of 13	NP_001334778.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13C	ENST00000618804.5	TSL:1 MANE Select	c.1427T>A	p.Leu476His	missense	Exon 12 of 14	ENSP00000481854.1
	FAM13C	ENST00000611933.4	TSL:1	c.1133T>A	p.Leu378His	missense	Exon 10 of 12	ENSP00000481830.1
	FAM13C	ENST00000951024.1		c.1493T>A	p.Leu498His	missense	Exon 13 of 15	ENSP00000621083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.059	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.4
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.19
Sift	Benign	0.035	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.43
MutPred		0.23		Loss of stability (P = 0.0585)
MVP		0.76
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.30
gMVP		0.44
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs193920897; hg19: chr10-61012664; COSMIC: COSV53252337; COSMIC: COSV53252337;