chr11-71527409-G-T

Position:

• chr11-71527409-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012503.2(KRTAP5-7):​c.109G>T​(p.Val37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: KRTAP5-7 NM_001012503.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.165

Genes affected

KRTAP5-7 (HGNC:23602): (keratin associated protein 5-7) Predicted to be located in cytosol. [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=0.03531304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-7	NM_001012503.2	c.109G>T	p.Val37Leu	missense_variant	1/1	ENST00000398536.6	NP_001012521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-7	ENST00000398536.6	c.109G>T	p.Val37Leu	missense_variant	1/1	6	NM_001012503.2	ENSP00000417330.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 142

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2023

The c.109G>T (p.V37L) alteration is located in exon 1 (coding exon 1) of the KRTAP5-7 gene. This alteration results from a G to T substitution at nucleotide position 109, causing the valine (V) at amino acid position 37 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.3
DANN	Benign	0.74
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.052
Sift	Benign	0.42	T
Sift4G	Benign	0.72	T
Polyphen		0.15	B
Vest4		0.072
MutPred		0.21		Loss of glycosylation at S34 (P = 0.1251);
MVP		0.030
MPC		0.011
ClinPred		0.086	T
GERP RS		0.39
Varity_R		0.055
gMVP		0.020

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: chr11-71238455;