NM_173853.4:c.262C>T

Variant names:

• chr2-27442890-C-T
• rs781428661
• NM_173853.4:c.262C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173853.4(KRTCAP3):​c.262C>T​(p.Arg88Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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: 0.0000034 (0 hom.)
• Consequence: KRTCAP3 NM_173853.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09831771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTCAP3	NM_173853.4	c.262C>T	p.Arg88Cys	missense_variant	Exon 3 of 7	ENST00000288873.7	NP_776252.2
KRTCAP3	NM_001168364.2	c.262C>T	p.Arg88Cys	missense_variant	Exon 3 of 7		NP_001161836.1
KRTCAP3	NM_001321325.2	c.262C>T	p.Arg88Cys	missense_variant	Exon 3 of 7		NP_001308254.1
KRTCAP3	XM_047443704.1	c.262C>T	p.Arg88Cys	missense_variant	Exon 3 of 6		XP_047299660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTCAP3	ENST00000288873.7	c.262C>T	p.Arg88Cys	missense_variant	Exon 3 of 7	1	NM_173853.4	ENSP00000288873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460826 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726776

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.088	T;T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.67	T;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L;L;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.077	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.13
MutPred		0.43		Loss of glycosylation at P89 (P = 0.1088);Loss of glycosylation at P89 (P = 0.1088);.;
MVP		0.19
MPC		0.18
ClinPred		0.47	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs781428661; hg19: chr2-27665757;