21-30430727-G-A

Variant names:

• chr21-30430727-G-A
• rs148941861
• NM_181600.3:c.452G>A

Variant summary

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

The NM_181600.3(KRTAP13-4):​c.452G>A​(p.Cys151Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 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. C151F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRTAP13-4 NM_181600.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 0 publications found

Genes affected

KRTAP13-4 (HGNC:18926): (keratin associated protein 13-4) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC105372772 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181600.3. 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
	KRTAP13-4	NM_181600.3	MANE Select	c.452G>A	p.Cys151Tyr	missense	Exon 1 of 1	NP_853631.1	Q3LI77

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP13-4	ENST00000334068.4	TSL:6 MANE Select	c.452G>A	p.Cys151Tyr	missense	Exon 1 of 1	ENSP00000334834.2	Q3LI77

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250926 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460194 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726158

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.0000449 AC: 2 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110824

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.4
DANN	Benign	0.69
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0041	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.030
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Benign	0.10
Sift	Benign	0.16	T
Sift4G	Benign	0.19	T
Polyphen		0.28	B
Vest4		0.18
MutPred		0.95		Gain of catalytic residue at I150 (P = 0.186)
MVP		0.040
MPC		0.059
ClinPred		0.14	T
GERP RS		-0.69
PromoterAI		-0.0072	Neutral
Varity_R		0.17
gMVP		0.20
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: rs148941861; hg19: chr21-31803045; COSMIC: COSV61879492; COSMIC: COSV61879492;