chr2-27443528-G-C

Variant names:

• chr2-27443528-G-C
• rs747449052
• NM_173853.4:c.611G>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.611G>C​(p.Gly204Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,820 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: 0.000023 (0 hom.)
• Consequence: KRTCAP3 NM_173853.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=0.021116555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTCAP3	NM_173853.4	c.611G>C	p.Gly204Ala	missense_variant	Exon 5 of 7	ENST00000288873.7	NP_776252.2
KRTCAP3	NM_001168364.2	c.611G>C	p.Gly204Ala	missense_variant	Exon 5 of 7		NP_001161836.1
KRTCAP3	NM_001321325.2	c.611G>C	p.Gly204Ala	missense_variant	Exon 5 of 7		NP_001308254.1
KRTCAP3	XM_047443704.1	c.611G>C	p.Gly204Ala	missense_variant	Exon 5 of 6		XP_047299660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTCAP3	ENST00000288873.7	c.611G>C	p.Gly204Ala	missense_variant	Exon 5 of 7	1	NM_173853.4	ENSP00000288873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000318 AC: 8 AN: 251226 Hom.: 0 AF XY: 0.0000589 AC XY: 8 AN XY: 135756

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: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461820 Hom.: 0 Cov.: 32 AF XY: 0.0000399 AC XY: 29 AN XY: 727214

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: 0.000383

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.22
DANN	Benign	0.60
DEOGEN2	Benign	0.0069	T;T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.76	T;.;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.021	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.61	N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.60	T;T;T;T
Sift4G	Benign	0.64	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.15
MutPred		0.21		Gain of helix (P = 0.027);Gain of helix (P = 0.027);.;.;
MVP		0.15
MPC		0.14
ClinPred		0.016	T
GERP RS		-10
Varity_R		0.045
gMVP		0.16

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: rs747449052; hg19: chr2-27666395;