21-30491780-C-T

Variant names:

• chr21-30491780-C-T
• rs145653137
• NM_181609.4:c.178G>A

Variant summary

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

The NM_181609.4(KRTAP19-3):​c.178G>A​(p.Gly60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. G60A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000070 (0 hom.)
• Consequence: KRTAP19-3 NM_181609.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0820
• Publications: 5 publications found

Genes affected

KRTAP19-3 (HGNC:18938): (keratin associated protein 19-3) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000303806 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.016915172).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181609.4. 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
	KRTAP19-3	NM_181609.4	MANE Select	c.178G>A	p.Gly60Arg	missense	Exon 1 of 1	NP_853640.1	Q7Z4W3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP19-3	ENST00000334063.6	TSL:6 MANE Select	c.178G>A	p.Gly60Arg	missense	Exon 1 of 1	ENSP00000386376.2	Q7Z4W3
	ENSG00000303806	ENST00000797282.1		n.118-7190C>T		intron	N/A
	ENSG00000303806	ENST00000797283.1		n.118-9216C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152052 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000143 AC: 36 AN: 251488 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00130

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000698 AC: 102 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.0000646 AC XY: 47 AN XY: 727236

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000932 AC: 37 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0000522 AC: 58 AN: 1111984

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74394

African (AFR) AF: 0.00 AC: 0 AN: 41506

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000813 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000165 AC: 20

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	-0.50	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.59
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.082
PROVEAN	Benign	0.67	N
REVEL	Benign	0.094
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.012	D
Polyphen		0.76	P
Vest4		0.26
MutPred		0.22		Gain of methylation at G60 (P = 0.0079)
MVP		0.22
MPC		0.043
ClinPred		0.052	T
GERP RS		-0.36
PromoterAI		-0.0078	Neutral
Varity_R		0.14
gMVP		0.056
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: rs145653137; hg19: chr21-31864098;