11-1584579-G-A

Variant names:

• chr11-1584579-G-A
• rs140869795
• NM_001005922.1:c.671C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005922.1(KRTAP5-1):​c.671C>T​(p.Ala224Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,613,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A224E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00200
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0072728395).

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.671C>T	p.Ala224Val	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11511G>A		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.671C>T	p.Ala224Val	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11511G>A		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12669G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000297 AC: 45 AN: 151770 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.000963

GnomAD2 exomes AF: 0.000390 AC: 98 AN: 251366 AF XY: 0.000353

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00417

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000221 AC: 323 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.000217 AC XY: 158 AN XY: 727242

African (AFR) AF: 0.000448 AC: 15 AN: 33480

American (AMR) AF: 0.000738 AC: 33 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00555 AC: 145 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000782 AC: 87 AN: 1112002

Other (OTH) AF: 0.000679 AC: 41 AN: 60392

GnomAD4 genome AF: 0.000297 AC: 45 AN: 151770 Hom.: 0 Cov.: 31 AF XY: 0.000243 AC XY: 18 AN XY: 74102

African (AFR) AF: 0.000267 AC: 11 AN: 41274

American (AMR) AF: 0.000525 AC: 8 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67958

Other (OTH) AF: 0.000963 AC: 2 AN: 2076

Alfa AF: 0.000447 Hom.: 0

Bravo AF: 0.000416

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000329 AC: 40

EpiCase AF: 0.00

EpiControl AF: 0.000356

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	-0.57	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.2
DANN	Benign	0.86
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0067	N
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-0.0020
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.050
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.49	T
Polyphen		0.68	P
Vest4		0.14
MVP		0.11
MPC		0.041
ClinPred		0.013	T
GERP RS		1.4
Varity_R		0.051
gMVP		0.0093
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: rs140869795; hg19: chr11-1605809; COSMIC: COSV66299065;