rs144891171

Variant names:

• chr21-30487292-G-A
• rs144891171
• NM_181608.2:c.57C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-30487292-G-A
• chr21-30487292-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_181608.2(KRTAP19-2):​c.57C>T​(p.Cys19Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000893 in 1,614,000 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (2 hom.)
• Consequence: KRTAP19-2 NM_181608.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.107

Genes affected

KRTAP19-2 (HGNC:18937): (keratin associated protein 19-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 21-30487292-G-A is Benign according to our data. Variant chr21-30487292-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3289674.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.107 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP19-2	NM_181608.2	c.57C>T	p.Cys19Cys	synonymous_variant	Exon 1 of 1	ENST00000334055.5	NP_853639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP19-2	ENST00000334055.5	c.57C>T	p.Cys19Cys	synonymous_variant	Exon 1 of 1	6	NM_181608.2	ENSP00000335660.3

Frequencies

GnomAD3 genomes AF: 0.000763 AC: 116 AN: 151992 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.000756 AC: 190 AN: 251440 Hom.: 1 AF XY: 0.000721 AC XY: 98 AN XY: 135888

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.00137

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000907 AC: 1326 AN: 1461890 Hom.: 2 Cov.: 30 AF XY: 0.000839 AC XY: 610 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000425

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000693

Gnomad4 NFE exome AF: 0.00109

Gnomad4 OTH exome AF: 0.000894

GnomAD4 genome AF: 0.000763 AC: 116 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.000686 AC XY: 51 AN XY: 74358

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00129

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.000777 Hom.: 0

Bravo AF: 0.000638

EpiCase AF: 0.000763

EpiControl AF: 0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 05, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.5
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs144891171; hg19: chr21-31859611; COSMIC: COSV100477540; COSMIC: COSV100477540;