chr2-27442758-C-A

Variant names:

• chr2-27442758-C-A
• NM_173853.4:c.208C>A

Variant summary

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

The NM_173853.4(KRTCAP3):​c.208C>A​(p.Leu70Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,252 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KRTCAP3 NM_173853.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16

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.208C>A	p.Leu70Met	missense_variant	Exon 2 of 7	ENST00000288873.7	NP_776252.2
KRTCAP3	NM_001168364.2	c.208C>A	p.Leu70Met	missense_variant	Exon 2 of 7		NP_001161836.1
KRTCAP3	NM_001321325.2	c.208C>A	p.Leu70Met	missense_variant	Exon 2 of 7		NP_001308254.1
KRTCAP3	XM_047443704.1	c.208C>A	p.Leu70Met	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.208C>A	p.Leu70Met	missense_variant	Exon 2 of 7	1	NM_173853.4	ENSP00000288873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457252 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 724830

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.00015	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.78	T;.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.72
MutPred		0.48		Loss of catalytic residue at L70 (P = 0.1006);Loss of catalytic residue at L70 (P = 0.1006);.;
MVP		0.44
MPC		0.56
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.57

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: chr2-27665625;