21-30319774-C-T

Variant names:

• chr21-30319774-C-T
• rs139698291
• NM_203405.2:c.262G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_203405.2(KRTAP26-1):​c.262G>A​(p.Val88Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,682 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (1 hom.)
• Consequence: KRTAP26-1 NM_203405.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23
• Publications: 1 publications found

Genes affected

KRTAP26-1 (HGNC:33760): (keratin associated protein 26-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18088782).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203405.2. 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
	KRTAP26-1	NM_203405.2	MANE Select	c.262G>A	p.Val88Met	missense	Exon 1 of 1	NP_981950.1	Q6PEX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP26-1	ENST00000360542.5	TSL:6 MANE Select	c.262G>A	p.Val88Met	missense	Exon 1 of 1	ENSP00000353742.3	Q6PEX3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250656 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000452 AC: 66 AN: 1461540 Hom.: 1 Cov.: 32 AF XY: 0.0000550 AC XY: 40 AN XY: 727062

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111868

Other (OTH) AF: 0.0000663 AC: 4 AN: 60364

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

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: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000193 Hom.: 0

Bravo AF: 0.0000453

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	0.17
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.069
Sift	Benign	0.041	D
Sift4G	Uncertain	0.013	D
Polyphen		0.95	P
Vest4		0.24
MVP		0.29
MPC		0.26
ClinPred		0.17	T
GERP RS		3.4
Varity_R		0.039
gMVP		0.060
Mutation Taster		=97/3	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: rs139698291; hg19: chr21-31692092; COSMIC: COSV100860385;