21-30282310-T-A

Position:

• chr21-30282310-T-A

Variant summary

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

The NM_001085455.3(KRTAP24-1):​c.623A>T​(p.Tyr208Phe) 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. 15/21 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: KRTAP24-1 NM_001085455.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.273

Genes affected

KRTAP24-1 (HGNC:33902): (keratin associated protein 24-1) Predicted to enable structural molecule activity. 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=0.08550683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP24-1	NM_001085455.3	c.623A>T	p.Tyr208Phe	missense_variant	1/1	ENST00000340345.6	NP_001078924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP24-1	ENST00000340345.6	c.623A>T	p.Tyr208Phe	missense_variant	1/1	6	NM_001085455.3	ENSP00000339238.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Feb 16, 2023

The c.623A>T (p.Y208F) alteration is located in exon 1 (coding exon 1) of the KRTAP24-1 gene. This alteration results from a A to T substitution at nucleotide position 623, causing the tyrosine (Y) at amino acid position 208 to be replaced by a phenylalanine (F). 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	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.3
DANN	Benign	0.14
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.017
Sift	Benign	0.51	T
Sift4G	Benign	1.0	T
Polyphen		0.28	B
Vest4		0.12
MutPred		0.59		Gain of sheet (P = 0.0827);
MVP		0.076
MPC		0.013
ClinPred		0.067	T
GERP RS		0.22
Varity_R		0.058
gMVP		0.026

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr21-31654628; COSMIC: COSV105225448;