NM_173853.4:c.203C>G

Variant names:

• chr2-27442753-C-G
• rs144811599
• NM_173853.4:c.203C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173853.4(KRTCAP3):​c.203C>G​(p.Ser68Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,456,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: KRTCAP3 NM_173853.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

Genes affected

KRTCAP3 (HGNC:28943): (keratinocyte associated protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTCAP3	NM_173853.4	c.203C>G	p.Ser68Trp	missense_variant	Exon 2 of 7	ENST00000288873.7	NP_776252.2
KRTCAP3	NM_001168364.2	c.203C>G	p.Ser68Trp	missense_variant	Exon 2 of 7		NP_001161836.1
KRTCAP3	NM_001321325.2	c.203C>G	p.Ser68Trp	missense_variant	Exon 2 of 7		NP_001308254.1
KRTCAP3	XM_047443704.1	c.203C>G	p.Ser68Trp	missense_variant	Exon 2 of 6		XP_047299660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTCAP3	ENST00000288873.7	c.203C>G	p.Ser68Trp	missense_variant	Exon 2 of 7	1	NM_173853.4	ENSP00000288873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000409 AC: 10 AN: 244444 Hom.: 0 AF XY: 0.0000676 AC XY: 9 AN XY: 133086

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000444

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000906

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1456856 Hom.: 0 Cov.: 33 AF XY: 0.0000152 AC XY: 11 AN XY: 724526

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ExAC AF: 0.0000414 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;.
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Pathogenic	0.58	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.7	D;D;D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.80
MutPred		0.64		Loss of glycosylation at S68 (P = 0.0193);Loss of glycosylation at S68 (P = 0.0193);.;
MVP		0.68
MPC		0.71
ClinPred		0.94	D
GERP RS		5.0
Varity_R		0.84
gMVP		0.87

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: rs144811599; hg19: chr2-27665620; COSMIC: COSV105821523; COSMIC: COSV105821523;