chr10-59254368-G-A

Position:

• chr10-59254368-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198215.4(FAM13C):​c.1312C>T​(p.Pro438Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FAM13C NM_198215.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.276325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM13C	NM_198215.4	c.1312C>T	p.Pro438Ser	missense_variant	11/14	ENST00000618804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM13C	ENST00000618804.5	c.1312C>T	p.Pro438Ser	missense_variant	11/14	1	NM_198215.4	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1401508 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 696864

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.26e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Dec 06, 2021

The c.1312C>T (p.P438S) alteration is located in exon 11 (coding exon 11) of the FAM13C gene. This alteration results from a C to T substitution at nucleotide position 1312, causing the proline (P) at amino acid position 438 to be replaced by a serine (S). 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	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;.;.;.;.;.;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.28	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	L;.;.;.;.;.;.;L
MutationTaster	Benign	0.98	D;D;D;D;D;D;D;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.0	.;.;.;.;.;N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.011	.;.;.;.;.;D;D;D
Sift4G	Uncertain	0.043	D;T;D;D;D;T;D;D
Polyphen		1.0	D;.;.;.;D;.;D;P
Vest4		0.23
MutPred		0.41		Gain of phosphorylation at P438 (P = 0.0485);.;.;.;.;.;Gain of phosphorylation at P438 (P = 0.0485);Gain of phosphorylation at P438 (P = 0.0485);
MVP		0.69
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.098
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-61014128;