2-27443237-G-A

Variant names:

• chr2-27443237-G-A
• NM_173853.4:c.437G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173853.4(KRTCAP3):​c.437G>A​(p.Gly146Glu) 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. 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: 2.75

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3719737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTCAP3	NM_173853.4	c.437G>A	p.Gly146Glu	missense_variant	Exon 4 of 7	ENST00000288873.7	NP_776252.2
KRTCAP3	NM_001168364.2	c.437G>A	p.Gly146Glu	missense_variant	Exon 4 of 7		NP_001161836.1
KRTCAP3	NM_001321325.2	c.437G>A	p.Gly146Glu	missense_variant	Exon 4 of 7		NP_001308254.1
KRTCAP3	XM_047443704.1	c.437G>A	p.Gly146Glu	missense_variant	Exon 4 of 6		XP_047299660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTCAP3	ENST00000288873.7	c.437G>A	p.Gly146Glu	missense_variant	Exon 4 of 7	1	NM_173853.4	ENSP00000288873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.437G>A (p.G146E) alteration is located in exon 4 (coding exon 4) of the KRTCAP3 gene. This alteration results from a G to A substitution at nucleotide position 437, causing the glycine (G) at amino acid position 146 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T;.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.22	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.97	D;D;.
Vest4		0.67
MutPred		0.27		Gain of solvent accessibility (P = 0.0074);Gain of solvent accessibility (P = 0.0074);.;
MVP		0.30
MPC		0.69
ClinPred		0.86	D
GERP RS		4.0
Varity_R		0.13
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: chr2-27666104; COSMIC: COSV51995829; COSMIC: COSV51995829;