rs199522805

Variant names:

• chr21-30480263-C-A
• rs199522805
• NM_181607.3:c.55G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-30480263-C-A
• chr21-30480263-C-T

Variant summary

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

The NM_181607.3(KRTAP19-1):​c.55G>T​(p.Gly19Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,614,164 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. 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. G19S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: KRTAP19-1 NM_181607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013338685).

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.55G>T	p.Gly19Cys	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.55G>T	p.Gly19Cys	missense	Exon 1 of 1	ENSP00000375108.2	Q8IUB9
	ENSG00000303806	ENST00000797282.1		n.117+4319C>A		intron	N/A
	ENSG00000303806	ENST00000797283.1		n.117+4319C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000585 AC: 89 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000159 AC: 40 AN: 251336 AF XY: 0.000140

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.0000578

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: 0.000163

GnomAD4 exome AF: 0.0000739 AC: 108 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.0000688 AC XY: 50 AN XY: 727240

African (AFR) AF: 0.00287 AC: 96 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

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: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.000166 AC: 10 AN: 60394

GnomAD4 genome AF: 0.000584 AC: 89 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74460

African (AFR) AF: 0.00200 AC: 83 AN: 41562

American (AMR) AF: 0.000327 AC: 5 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000280 Hom.: 0

Bravo AF: 0.000812

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000222 AC: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.034	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.34
PROVEAN	Pathogenic	-9.0	D
REVEL	Benign	0.075
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.41
MVP		0.17
MPC		0.12
ClinPred		0.14	T
GERP RS		1.7
PromoterAI		0.017	Neutral
Varity_R		0.63
gMVP		0.092
Mutation Taster		=98/2	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: rs199522805; hg19: chr21-31852582;