21-30289390-T-G

Position:

• chr21-30289390-T-G

Variant summary

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

The NM_001128598.1(KRTAP25-1):​c.101A>C​(p.Gln34Pro) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP25-1 NM_001128598.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.48

Genes affected

KRTAP25-1 (HGNC:34003): (keratin associated protein 25-1) 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=0.08476582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP25-1	NM_001128598.1	c.101A>C	p.Gln34Pro	missense_variant	1/1	ENST00000416044.1	NP_001122070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP25-1	ENST00000416044.1	c.101A>C	p.Gln34Pro	missense_variant	1/1	6	NM_001128598.1	ENSP00000398619.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 13, 2023

The c.101A>C (p.Q34P) alteration is located in exon 1 (coding exon 1) of the KRTAP25-1 gene. This alteration results from a A to C substitution at nucleotide position 101, causing the glutamine (Q) at amino acid position 34 to be replaced by a proline (P). 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	0.091
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.1
DANN	Benign	0.79
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.12
Sift	Benign	0.055	T
Sift4G	Benign	0.093	T
Polyphen		0.040	B
Vest4		0.40
MutPred		0.27		Loss of sheet (P = 0.0054);
MVP		0.030
ClinPred		0.057	T
GERP RS		-3.4
Varity_R		0.64
gMVP		0.052

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: chr21-31661708;