2-27444241-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_173853.4(KRTCAP3):c.*61G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 645,062 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (15 hom.)
• Consequence: KRTCAP3 NM_173853.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.169

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 2-27444241-G-A is Benign according to our data. Variant chr2-27444241-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1211369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1845/152244) while in subpopulation AFR AF= 0.0426 (1768/41536). AF 95% confidence interval is 0.0409. There are 39 homozygotes in gnomad4. There are 853 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTCAP3	NM_173853.4	c.*61G>A		3_prime_UTR_variant	7/7	ENST00000288873.7
KRTCAP3	NM_001321325.2	c.*58G>A		3_prime_UTR_variant	7/7
KRTCAP3	XM_047443704.1	c.*185G>A		3_prime_UTR_variant	6/6
KRTCAP3	NM_001168364.2	c.*5+180G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTCAP3	ENST00000288873.7	c.*61G>A		3_prime_UTR_variant	7/7	1	NM_173853.4	P1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1831 AN: 152126 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00622

GnomAD4 exome AF: 0.00153 AC: 756 AN: 492818 Hom.: 15 Cov.: 6 AF XY: 0.00121 AC XY: 313 AN XY: 259712

Gnomad4 AFR exome AF: 0.0462

Gnomad4 AMR exome AF: 0.00263

Gnomad4 ASJ exome AF: 0.000140

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000778

Gnomad4 OTH exome AF: 0.00264

GnomAD4 genome AF: 0.0121 AC: 1845 AN: 152244 Hom.: 39 Cov.: 32 AF XY: 0.0115 AC XY: 853 AN XY: 74436

Gnomad4 AFR AF: 0.0426

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00268 Hom.: 6

Bravo AF: 0.0136

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	4.3
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10208616; hg19: chr2-27667108;