10-59268656-C-T

Variant names:

• chr10-59268656-C-T
• rs370898940
• NM_198215.4:c.839G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_198215.4(FAM13C):​c.839G>A​(p.Gly280Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,613,170 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: FAM13C NM_198215.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59
• Publications: 2 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1314539).

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.839G>A	p.Gly280Asp	missense	Exon 8 of 14	NP_937858.2	Q8NE31-1
	FAM13C	NM_001347852.2		c.839G>A	p.Gly280Asp	missense	Exon 8 of 13	NP_001334781.1	B7Z2K3
	FAM13C	NM_001347849.2		c.839G>A	p.Gly280Asp	missense	Exon 8 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.839G>A	p.Gly280Asp	missense	Exon 8 of 14	ENSP00000481854.1	Q8NE31-1
	FAM13C	ENST00000611933.4	TSL:1	c.839G>A	p.Gly280Asp	missense	Exon 8 of 12	ENSP00000481830.1	Q8NE31-3
	FAM13C	ENST00000951024.1		c.839G>A	p.Gly280Asp	missense	Exon 8 of 15	ENSP00000621083.1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000108 AC: 27 AN: 250622 AF XY: 0.0000960

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000176 AC: 257 AN: 1460854 Hom.: 0 Cov.: 30 AF XY: 0.000171 AC XY: 124 AN XY: 726704

African (AFR) AF: 0.0000299 AC: 1 AN: 33434

American (AMR) AF: 0.000201 AC: 9 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5298

European-Non Finnish (NFE) AF: 0.000216 AC: 240 AN: 1111744

Other (OTH) AF: 0.0000995 AC: 6 AN: 60304

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74460

African (AFR) AF: 0.0000481 AC: 2 AN: 41564

American (AMR) AF: 0.000523 AC: 8 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000147 Hom.: 0

Bravo AF: 0.000170

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000382

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.0015	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.29	N
PhyloP100		2.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.15
Sift	Benign	0.49	T
Sift4G	Benign	0.68	T
Polyphen		0.87	P
Vest4		0.14
MVP		0.81
ClinPred		0.049	T
GERP RS		5.2
Varity_R		0.095
gMVP		0.12
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs370898940; hg19: chr10-61028416; COSMIC: COSV53247507; COSMIC: COSV53247507;