10-59254404-C-T

Variant names:

• chr10-59254404-C-T
• rs1250440604
• NM_198215.4:c.1276G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198215.4(FAM13C):​c.1276G>A​(p.Asp426Asn) 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM13C NM_198215.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM13C	NM_198215.4	c.1276G>A	p.Asp426Asn	missense_variant	Exon 11 of 14	ENST00000618804.5	NP_937858.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM13C	ENST00000618804.5	c.1276G>A	p.Asp426Asn	missense_variant	Exon 11 of 14	1	NM_198215.4	ENSP00000481854.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000451 AC: 1 AN: 221606 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 120632

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000963

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1405960 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 698780

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: 0.00

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

Feb 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1276G>A (p.D426N) alteration is located in exon 11 (coding exon 11) of the FAM13C gene. This alteration results from a G to A substitution at nucleotide position 1276, causing the aspartic acid (D) at amino acid position 426 to be replaced by an asparagine (N). 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	0.32
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T;.;.;.;.;.;.;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.57	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.0086	T
MutationAssessor	Uncertain	2.6	M;.;.;.;.;.;.;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.5	.;.;.;.;.;D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	.;.;.;.;.;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;D;.;D;D
Vest4		0.68
MutPred		0.34		Gain of MoRF binding (P = 0.0539);.;.;.;.;.;Gain of MoRF binding (P = 0.0539);Gain of MoRF binding (P = 0.0539);
MVP		0.83
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.50
gMVP		0.83

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

LitVar

Other links and lift over

dbSNP: rs1250440604; hg19: chr10-61014164; COSMIC: COSV104587570;