21-30590277-G-A

Variant names:

• chr21-30590277-G-A
• NM_001164434.1:c.98C>T

Variant summary

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

The NM_001164434.1(KRTAP22-2):​c.98C>T​(p.Ser33Phe) 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. 11/17 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: KRTAP22-2 NM_001164434.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.483

Genes affected

KRTAP22-2 (HGNC:37091): (keratin associated protein 22-2) Predicted to be located in intermediate filament. [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=0.12107375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP22-2	NM_001164434.1	c.98C>T	p.Ser33Phe	missense_variant	Exon 1 of 1	ENST00000382830.2	NP_001157906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP22-2	ENST00000382830.2	c.98C>T	p.Ser33Phe	missense_variant	Exon 1 of 1	6	NM_001164434.1	ENSP00000372281.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.98C>T (p.S33F) alteration is located in exon 1 (coding exon 1) of the KRTAP22-2 gene. This alteration results from a C to T substitution at nucleotide position 98, causing the serine (S) at amino acid position 33 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.053	N
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.047
Sift4G	Benign	0.71	T
Vest4		0.15
MutPred		0.32		Gain of sheet (P = 0.0477);
MVP		0.061
ClinPred		0.21	T
GERP RS		2.0
Varity_R		0.23
gMVP		0.042

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: chr21-31962596;