2-27444034-C-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.701C>T(p.Ala234Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTCAP3 NM_173853.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.177

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=0.068974495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTCAP3	NM_173853.4	c.701C>T	p.Ala234Val	missense_variant	6/7	ENST00000288873.7
KRTCAP3	NM_001168364.2	c.701C>T	p.Ala234Val	missense_variant	6/7
KRTCAP3	NM_001321325.2	c.701C>T	p.Ala234Val	missense_variant	6/7
KRTCAP3	XM_047443704.1	c.701C>T	p.Ala234Val	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTCAP3	ENST00000288873.7	c.701C>T	p.Ala234Val	missense_variant	6/7	1	NM_173853.4	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2022

The c.701C>T (p.A234V) alteration is located in exon 6 (coding exon 6) of the KRTCAP3 gene. This alteration results from a C to T substitution at nucleotide position 701, causing the alanine (A) at amino acid position 234 to be replaced by a valine (V). 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	Benign	0.074
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	3.7
Dann	Benign	0.85
DEOGEN2	Benign	0.011	T;T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.49	T;.;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M;M;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.57	N;N;N;N
REVEL	Benign	0.045
Sift	Uncertain	0.019	D;D;D;D
Sift4G	Benign	0.48	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.070
MutPred		0.19		Gain of MoRF binding (P = 0.122);Gain of MoRF binding (P = 0.122);.;.;
MVP		0.061
MPC		0.13
ClinPred		0.041	T
GERP RS		0.15
Varity_R		0.029
gMVP		0.075

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr2-27666901;