21-30561270-T-C

Position:

• chr21-30561270-T-C

Variant summary

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

The NM_181614.3(KRTAP19-7):​c.20A>G​(p.Tyr7Cys) 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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP19-7 NM_181614.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.117

Genes affected

KRTAP19-7 (HGNC:18942): (keratin associated protein 19-7) 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=0.11715487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP19-7	NM_181614.3	c.20A>G	p.Tyr7Cys	missense_variant	1/1	ENST00000334849.2	NP_853645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP19-7	ENST00000334849.2	c.20A>G	p.Tyr7Cys	missense_variant	1/1	6	NM_181614.3	ENSP00000334696.2

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

Aug 26, 2024

The c.20A>G (p.Y7C) alteration is located in exon 1 (coding exon 1) of the KRTAP19-7 gene. This alteration results from a A to G substitution at nucleotide position 20, causing the tyrosine (Y) at amino acid position 7 to be replaced by a cysteine (C). 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	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.30
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.062
Sift4G	Uncertain	0.055	T
Polyphen		0.011	B
Vest4		0.32
MutPred		0.14		Loss of sheet (P = 0.0315);
MVP		0.30
MPC		0.023
ClinPred		0.62	D
GERP RS		1.5
Varity_R		0.74
gMVP		0.073

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: chr21-31933589;