chr10-59270108-G-T

Position:

• chr10-59270108-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198215.4(FAM13C):​c.594C>A​(p.Asp198Glu) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM13C NM_198215.4 missense, splice_region
• Scores: Splicing: ADA: 0.0007560
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.723

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037675112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM13C	NM_198215.4	c.594C>A	p.Asp198Glu	missense_variant, splice_region_variant	7/14	ENST00000618804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM13C	ENST00000618804.5	c.594C>A	p.Asp198Glu	missense_variant, splice_region_variant	7/14	1	NM_198215.4	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.594C>A (p.D198E) alteration is located in exon 7 (coding exon 7) of the FAM13C gene. This alteration results from a C to A substitution at nucleotide position 594, causing the aspartic acid (D) at amino acid position 198 to be replaced by a glutamic acid (E). 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
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.0
DANN	Benign	0.93
DEOGEN2	Benign	0.0016	T;.;.;.;.;.;.;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.70	T;T;T;T;T;T;T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.038	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.;.;L;.;.;L
MutationTaster	Benign	0.99	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.1	.;.;.;.;.;N;N;N
REVEL	Benign	0.10
Sift	Benign	1.0	.;.;.;.;.;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T
Polyphen		0.0020	B;.;.;.;B;.;B;B
Vest4		0.051
MutPred		0.12		Gain of glycosylation at T194 (P = 0.1557);.;.;.;Gain of glycosylation at T194 (P = 0.1557);.;Gain of glycosylation at T194 (P = 0.1557);Gain of glycosylation at T194 (P = 0.1557);
MVP		0.63
ClinPred		0.10	T
GERP RS		0.11
Varity_R		0.024
gMVP		0.048

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00076
dbscSNV1_RF	Benign	0.064
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-61029868;