rs768003210

Variant names:

• chr21-30480109-C-A
• rs768003210
• NM_181607.3:c.209G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-30480109-C-A
• chr21-30480109-C-G
• chr21-30480109-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181607.3(KRTAP19-1):​c.209G>T​(p.Gly70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 1,600,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: KRTAP19-1 NM_181607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.214
• Publications: 0 publications found

Genes affected

KRTAP19-1 (HGNC:18936): (keratin associated protein 19-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000303806 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12684947).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181607.3. 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
	KRTAP19-1	NM_181607.3	MANE Select	c.209G>T	p.Gly70Val	missense	Exon 1 of 1	NP_853638.1	Q8IUB9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP19-1	ENST00000390689.3	TSL:6 MANE Select	c.209G>T	p.Gly70Val	missense	Exon 1 of 1	ENSP00000375108.2	Q8IUB9
	ENSG00000303806	ENST00000797282.1		n.117+4165C>A		intron	N/A
	ENSG00000303806	ENST00000797283.1		n.117+4165C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151408 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: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251460 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1448792 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720738

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099754

Other (OTH) AF: 0.00 AC: 0 AN: 59960

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151408 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73978

African (AFR) AF: 0.00 AC: 0 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15236

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67468

Other (OTH) AF: 0.00 AC: 0 AN: 2076

ExAC AF: 0.00000825 AC: 1

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	-0.44	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.58
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.046	N
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.21
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.036
Sift4G	Pathogenic	0.0	D
Polyphen		0.78	P
Vest4		0.32
MutPred		0.30		Gain of sheet (P = 0.0049)
MVP		0.16
MPC		0.14
ClinPred		0.22	T
GERP RS		2.7
PromoterAI		-0.011	Neutral
Varity_R		0.43
gMVP		0.075
Mutation Taster		=98/2	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: rs768003210; hg19: chr21-31852428;