2-27442659-G-C

Variant names:

• chr2-27442659-G-C
• NM_173853.4:c.109G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173853.4(KRTCAP3):​c.109G>C​(p.Ala37Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,431,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000014 (0 hom.)
• Consequence: KRTCAP3 NM_173853.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTCAP3	NM_173853.4	c.109G>C	p.Ala37Pro	missense_variant	Exon 2 of 7	ENST00000288873.7	NP_776252.2
KRTCAP3	NM_001168364.2	c.109G>C	p.Ala37Pro	missense_variant	Exon 2 of 7		NP_001161836.1
KRTCAP3	NM_001321325.2	c.109G>C	p.Ala37Pro	missense_variant	Exon 2 of 7		NP_001308254.1
KRTCAP3	XM_047443704.1	c.109G>C	p.Ala37Pro	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.109G>C	p.Ala37Pro	missense_variant	Exon 2 of 7	1	NM_173853.4	ENSP00000288873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1431356 Hom.: 0 Cov.: 33 AF XY: 0.00000282 AC XY: 2 AN XY: 709138

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: 0.00000182

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	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T;.;T
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0030	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.68
MutPred		0.81		Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);.;
MVP		0.78
MPC		0.69
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.89
gMVP		0.88

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: chr2-27665526;