21-30541748-C-A

Variant names:

• chr21-30541748-C-A
• rs367932839
• NM_181612.3:c.86G>T

Variant summary

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

The NM_181612.3(KRTAP19-6):​c.86G>T​(p.Gly29Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000682 in 1,613,846 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. G29D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (1 hom.)
• Consequence: KRTAP19-6 NM_181612.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.984
• Publications: 0 publications found

Genes affected

KRTAP19-6 (HGNC:18941): (keratin associated protein 19-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000308278 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.06456962).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181612.3. 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
	KRTAP19-6	NM_181612.3	MANE Select	c.86G>T	p.Gly29Val	missense	Exon 1 of 1	NP_853643.1	Q3LI70

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP19-6	ENST00000334046.5	TSL:6 MANE Select	c.86G>T	p.Gly29Val	missense	Exon 1 of 1	ENSP00000375107.3	Q3LI70
	ENSG00000308278	ENST00000832954.1		n.124+10785C>A		intron	N/A
	ENSG00000308278	ENST00000832955.1		n.165+10785C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000115 AC: 29 AN: 251476 AF XY: 0.000110

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000761

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.0000623 AC: 91 AN: 1461688 Hom.: 1 Cov.: 32 AF XY: 0.0000688 AC XY: 50 AN XY: 727150

African (AFR) AF: 0.000239 AC: 8 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111830

Other (OTH) AF: 0.000960 AC: 58 AN: 60388

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74324

African (AFR) AF: 0.000266 AC: 11 AN: 41430

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000152 Hom.: 0

Bravo AF: 0.000132

ExAC AF: 0.0000824 AC: 10

Asia WGS AF: 0.00318 AC: 11 AN: 3478

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	0.18
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.0
DANN	Benign	0.68
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.98
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.053
Sift4G	Uncertain	0.0050	D
Polyphen		0.70	P
Vest4		0.39
MVP		0.46
MPC		0.29
ClinPred		0.092	T
GERP RS		2.1
PromoterAI		-0.0036	Neutral
Varity_R		0.38
gMVP		0.068
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: rs367932839; hg19: chr21-31914067;