10-59252971-G-T

Variant names:

• chr10-59252971-G-T
• rs147832265
• NM_198215.4:c.1360C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198215.4(FAM13C):​c.1360C>A​(p.Arg454Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R454C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM13C NM_198215.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 3 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.019861639).

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.1360C>A	p.Arg454Ser	missense	Exon 12 of 14	NP_937858.2	Q8NE31-1
	FAM13C	NM_001347852.2		c.1360C>A	p.Arg454Ser	missense	Exon 12 of 13	NP_001334781.1	B7Z2K3
	FAM13C	NM_001347849.2		c.1357C>A	p.Arg453Ser	missense	Exon 12 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.1360C>A	p.Arg454Ser	missense	Exon 12 of 14	ENSP00000481854.1	Q8NE31-1
	FAM13C	ENST00000611933.4	TSL:1	c.1066C>A	p.Arg356Ser	missense	Exon 10 of 12	ENSP00000481830.1	Q8NE31-3
	FAM13C	ENST00000951024.1		c.1426C>A	p.Arg476Ser	missense	Exon 13 of 15	ENSP00000621083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461510 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727054

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5546

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111932

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.21
DANN	Benign	0.36
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.46	N
PhyloP100		0.30
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.031
Sift	Benign	0.74	T
Sift4G	Benign	0.82	T
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.25		Gain of phosphorylation at R454 (P = 0.0079)
MVP		0.24
ClinPred		0.050	T
GERP RS		1.9
Varity_R		0.10
gMVP		0.20
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

dbSNP: rs147832265; hg19: chr10-61012731;