2-27442612-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173853.4(KRTCAP3):c.62T>C(p.Val21Ala) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V21M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTCAP3 NM_173853.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0650

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052691728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTCAP3	NM_173853.4	c.62T>C	p.Val21Ala	missense_variant	2/7	ENST00000288873.7
KRTCAP3	NM_001168364.2	c.62T>C	p.Val21Ala	missense_variant	2/7
KRTCAP3	NM_001321325.2	c.62T>C	p.Val21Ala	missense_variant	2/7
KRTCAP3	XM_047443704.1	c.62T>C	p.Val21Ala	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTCAP3	ENST00000288873.7	c.62T>C	p.Val21Ala	missense_variant	2/7	1	NM_173853.4	P1
KRTCAP3	ENST00000543753.5	c.62T>C	p.Val21Ala	missense_variant	2/7	5		P1
KRTCAP3	ENST00000407293.5	c.8T>C	p.Val3Ala	missense_variant	1/6	2
KRTCAP3	ENST00000453171.5	c.28+172T>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1412020 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 697612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Aug 16, 2021

The c.62T>C (p.V21A) alteration is located in exon 2 (coding exon 2) of the KRTCAP3 gene. This alteration results from a T to C substitution at nucleotide position 62, causing the valine (V) at amino acid position 21 to be replaced by an alanine (A). 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	0.076
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	12
Dann	Benign	0.88
DEOGEN2	Benign	0.0072	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.56	T;.;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.053	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.47	N;N;N
REVEL	Benign	0.015
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.13
MutPred		0.26		Loss of stability (P = 0.0491);Loss of stability (P = 0.0491);.;
MVP		0.055
MPC		0.17
ClinPred		0.10	T
GERP RS		-0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.028
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27665479;