10-59247656-T-G

Variant names:

• chr10-59247656-T-G
• NM_198215.4:c.1716A>C

Variant summary

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

The NM_198215.4(FAM13C):​c.1716A>C​(p.Leu572Phe) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM13C NM_198215.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.380

Genes affected

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

PHYHIPL (HGNC:29378): (phytanoyl-CoA 2-hydroxylase interacting protein like) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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.1716A>C	p.Leu572Phe	missense_variant	Exon 14 of 14	ENST00000618804.5	NP_937858.2
PHYHIPL	NM_032439.4	c.*2065T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000373880.9	NP_115815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM13C	ENST00000618804.5	c.1716A>C	p.Leu572Phe	missense_variant	Exon 14 of 14	1	NM_198215.4	ENSP00000481854.1
PHYHIPL	ENST00000373880.9	c.*2065T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_032439.4	ENSP00000362987.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1716A>C (p.L572F) alteration is located in exon 14 (coding exon 14) of the FAM13C gene. This alteration results from a A to C substitution at nucleotide position 1716, causing the leucine (L) at amino acid position 572 to be replaced by a phenylalanine (F). 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	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;.;.;.;.;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.63	D;D;D;D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.6	M;.;.;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.5	.;.;.;.;.;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	.;.;.;.;.;D
Sift4G	Uncertain	0.0040	D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;D;.
Vest4		0.64
MutPred		0.53		Loss of helix (P = 0.079);.;.;.;.;.;
MVP		0.54
ClinPred		0.98	D
GERP RS		1.0
Varity_R		0.39
gMVP		0.64

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: chr10-61007416;