11-1621822-C-A

Variant names:

• chr11-1621822-C-A
• rs1463586225
• NM_001347674.1:c.272G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001347674.1(KRTAP5-4):​c.272G>T​(p.Cys91Phe) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: KRTAP5-4 NM_001347674.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• Publications: 0 publications found

Genes affected

KRTAP5-4 (HGNC:23599): (keratin associated protein 5-4) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28933287).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347674.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-4	NM_001347674.1	MANE Select	c.272G>T	p.Cys91Phe	missense	Exon 1 of 1	NP_001334603.1	A8MUN0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-4	ENST00000399682.1	TSL:6 MANE Select	c.272G>T	p.Cys91Phe	missense	Exon 1 of 1	ENSP00000382590.1	A8MUN0

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.83
Eigen	Benign	-0.030
Eigen_PC	Benign	-0.079
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.00096	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.6
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.069
Sift	Uncertain	0.021	D
Sift4G	Pathogenic	0.0	D
Vest4		0.42
MVP		0.088
MPC		0.032
ClinPred		0.21	T
GERP RS		2.5
PromoterAI		0.012	Neutral
gMVP		0.016
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1463586225; hg19: chr11-1643052;