21-30372177-G-A

Variant names:

• chr21-30372177-G-A
• rs149187693
• NM_181621.4:c.37C>T

Variant summary

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

The NM_181621.4(KRTAP13-2):​c.37C>T​(p.Arg13Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000569 in 1,613,730 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 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. R13G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (1 hom.)
• Consequence: KRTAP13-2 NM_181621.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 3 publications found

Genes affected

KRTAP13-2 (HGNC:18923): (keratin associated protein 13-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.041012287).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181621.4. 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
	KRTAP13-2	NM_181621.4	MANE Select	c.37C>T	p.Arg13Cys	missense	Exon 1 of 1	NP_853652.1	Q52LG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP13-2	ENST00000399889.4	TSL:6 MANE Select	c.37C>T	p.Arg13Cys	missense	Exon 1 of 1	ENSP00000382777.2	Q52LG2

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000955

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000387 AC: 97 AN: 250610 AF XY: 0.000399

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000805

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000577 AC: 844 AN: 1461578 Hom.: 1 Cov.: 33 AF XY: 0.000586 AC XY: 426 AN XY: 727064

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86246

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53408

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.000720 AC: 800 AN: 1111798

Other (OTH) AF: 0.000348 AC: 21 AN: 60380

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.000511 AC XY: 38 AN XY: 74310

African (AFR) AF: 0.000121 AC: 5 AN: 41430

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.000955 AC: 65 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000691 Hom.: 0

Bravo AF: 0.000468

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000346 AC: 42

EpiCase AF: 0.000709

EpiControl AF: 0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.0
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.020
Sift	Benign	0.21	T
Sift4G	Benign	0.13	T
Polyphen		0.35	B
Vest4		0.19
MVP		0.12
MPC		0.050
ClinPred		0.039	T
GERP RS		0.036
PromoterAI		0.0096	Neutral
Varity_R		0.13
gMVP		0.032
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149187693; hg19: chr21-31744495;