10-59264163-A-C

Variant names:

• chr10-59264163-A-C
• NM_198215.4:c.946T>G

Variant summary

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

The NM_198215.4(FAM13C):​c.946T>G​(p.Ser316Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM13C NM_198215.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13C	NM_198215.4	MANE Select	c.946T>G	p.Ser316Ala	missense	Exon 9 of 14	NP_937858.2	Q8NE31-1
	FAM13C	NM_001347852.2		c.946T>G	p.Ser316Ala	missense	Exon 9 of 13	NP_001334781.1	B7Z2K3
	FAM13C	NM_001347849.2		c.946T>G	p.Ser316Ala	missense	Exon 9 of 13	NP_001334778.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13C	ENST00000618804.5	TSL:1 MANE Select	c.946T>G	p.Ser316Ala	missense	Exon 9 of 14	ENSP00000481854.1	Q8NE31-1
	FAM13C	ENST00000611933.4	TSL:1	c.942+4390T>G		intron	N/A	ENSP00000481830.1	Q8NE31-3
	FAM13C	ENST00000951024.1		c.946T>G	p.Ser316Ala	missense	Exon 9 of 15	ENSP00000621083.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	Uncertain	0.42
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.026	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.47
Sift	Benign	0.040	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.78	P
Vest4		0.32
MutPred		0.20		Loss of phosphorylation at S316 (P = 0.005)
MVP		0.80
ClinPred		0.87	D
GERP RS		5.8
Varity_R		0.28
gMVP		0.51
Mutation Taster		=74/26	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

hg19: chr10-61023923;