21-30337598-C-A

Position:

• chr21-30337598-C-A

Variant summary

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

The NM_001077711.1(KRTAP27-1):​c.71G>T​(p.Gly24Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP27-1 NM_001077711.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.380

Genes affected

KRTAP27-1 (HGNC:33864): (keratin associated protein 27-1) Predicted to be located in cytosol. [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=0.17438012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP27-1	NM_001077711.1	c.71G>T	p.Gly24Val	missense_variant	1/1	ENST00000382835.2	NP_001071179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP27-1	ENST00000382835.2	c.71G>T	p.Gly24Val	missense_variant	1/1		NM_001077711.1	ENSP00000372286	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

May 23, 2024

The c.71G>T (p.G24V) alteration is located in exon 1 (coding exon 1) of the KRTAP27-1 gene. This alteration results from a G to T substitution at nucleotide position 71, causing the glycine (G) at amino acid position 24 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.039
Sift	Benign	0.35	T
Sift4G	Benign	0.59	T
Polyphen		0.97	D
Vest4		0.38
MutPred		0.38		Loss of relative solvent accessibility (P = 0.0071);
MVP		0.19
MPC		0.15
ClinPred		0.53	D
GERP RS		-2.7
Varity_R		0.048
gMVP		0.074

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-31709916;