11-1584675-C-T

Variant names:

• chr11-1584675-C-T
• rs145691791
• NM_001005922.1:c.575G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005922.1(KRTAP5-1):​c.575G>A​(p.Gly192Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 979,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G192V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• Publications: 0 publications found

Genes affected

KRTAP5-1 (HGNC:23596): (keratin associated protein 5-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-AS1 (HGNC:27877): (KRTAP5-1/KRTAP5-2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12172845).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005922.1. 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
	KRTAP5-1	NM_001005922.1	MANE Select	c.575G>A	p.Gly192Glu	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11607C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-1	ENST00000382171.2	TSL:6 MANE Select	c.575G>A	p.Gly192Glu	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11607C>T		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12573C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 979988 Hom.: 0 Cov.: 53 AF XY: 0.00 AC XY: 0 AN XY: 498180

African (AFR) AF: 0.00 AC: 0 AN: 22808

American (AMR) AF: 0.00 AC: 0 AN: 38826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18570

East Asian (EAS) AF: 0.0000435 AC: 1 AN: 23006

South Asian (SAS) AF: 0.00 AC: 0 AN: 74658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3874

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 715562

Other (OTH) AF: 0.00 AC: 0 AN: 39662

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.66
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.012	N
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.4
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.033
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.25	T
Polyphen		0.042	B
Vest4		0.33
MutPred		0.21		Loss of glycosylation at S193 (P = 0.0644)
MVP		0.24
MPC		0.049
ClinPred		0.25	T
GERP RS		1.8
Varity_R		0.090
gMVP		0.010
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: rs145691791; hg19: chr11-1605905;