2-27442651-T-A

Variant names:

• chr2-27442651-T-A
• rs1664679383
• NM_173853.4:c.101T>A

Variant summary

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

The NM_173853.4(KRTCAP3):​c.101T>A​(p.Leu34Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,427,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: KRTCAP3 NM_173853.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.85

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTCAP3	NM_173853.4	c.101T>A	p.Leu34Gln	missense_variant	Exon 2 of 7	ENST00000288873.7	NP_776252.2
KRTCAP3	NM_001168364.2	c.101T>A	p.Leu34Gln	missense_variant	Exon 2 of 7		NP_001161836.1
KRTCAP3	NM_001321325.2	c.101T>A	p.Leu34Gln	missense_variant	Exon 2 of 7		NP_001308254.1
KRTCAP3	XM_047443704.1	c.101T>A	p.Leu34Gln	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.101T>A	p.Leu34Gln	missense_variant	Exon 2 of 7	1	NM_173853.4	ENSP00000288873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1427456 Hom.: 0 Cov.: 33 AF XY: 0.00000141 AC XY: 1 AN XY: 707078

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: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.101T>A (p.L34Q) alteration is located in exon 2 (coding exon 2) of the KRTCAP3 gene. This alteration results from a T to A substitution at nucleotide position 101, causing the leucine (L) at amino acid position 34 to be replaced by a glutamine (Q). 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	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;.;T
M_CAP	Pathogenic	0.49	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.55
MutPred		0.49		Gain of catalytic residue at L34 (P = 0.0369);Gain of catalytic residue at L34 (P = 0.0369);.;
MVP		0.73
MPC		0.61
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.81
gMVP		0.70

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: rs1664679383; hg19: chr2-27665518;