chr2-27444003-C-A

Variant names:

• chr2-27444003-C-A
• rs781492553
• NM_173853.4:c.670C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173853.4(KRTCAP3):​c.670C>A​(p.Gln224Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KRTCAP3 NM_173853.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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=0.13036484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTCAP3	NM_173853.4	c.670C>A	p.Gln224Lys	missense_variant	Exon 6 of 7	ENST00000288873.7	NP_776252.2
KRTCAP3	NM_001168364.2	c.670C>A	p.Gln224Lys	missense_variant	Exon 6 of 7		NP_001161836.1
KRTCAP3	NM_001321325.2	c.670C>A	p.Gln224Lys	missense_variant	Exon 6 of 7		NP_001308254.1
KRTCAP3	XM_047443704.1	c.670C>A	p.Gln224Lys	missense_variant	Exon 6 of 6		XP_047299660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTCAP3	ENST00000288873.7	c.670C>A	p.Gln224Lys	missense_variant	Exon 6 of 7	1	NM_173853.4	ENSP00000288873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251470 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135914

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461534 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727122

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.020	T;T;.;T
Eigen	Benign	-0.062
Eigen_PC	Benign	0.070
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.65	T;.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L;L;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.62	N;N;N;N
REVEL	Benign	0.086
Sift	Benign	0.15	T;T;T;T
Sift4G	Uncertain	0.049	D;D;D;D
Polyphen		0.0010	B;B;.;.
Vest4		0.19
MutPred		0.22		Gain of ubiquitination at Q224 (P = 0.0011);Gain of ubiquitination at Q224 (P = 0.0011);.;.;
MVP		0.21
MPC		0.17
ClinPred		0.39	T
GERP RS		4.9
Varity_R		0.19
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs781492553; hg19: chr2-27666870;