chr21-30487312-A-C

Variant names:

• chr21-30487312-A-C
• rs776584128
• NM_181608.2:c.37T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181608.2(KRTAP19-2):​c.37T>G​(p.Cys13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,772 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KRTAP19-2 NM_181608.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.44
• Publications: 0 publications found

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]

ENSG00000303806 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029264897).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181608.2. 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
	KRTAP19-2	NM_181608.2	MANE Select	c.37T>G	p.Cys13Gly	missense	Exon 1 of 1	NP_853639.1	Q3LHN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP19-2	ENST00000334055.5	TSL:6 MANE Select	c.37T>G	p.Cys13Gly	missense	Exon 1 of 1	ENSP00000335660.3	Q3LHN2
	ENSG00000303806	ENST00000797282.1		n.117+11368A>C		intron	N/A
	ENSG00000303806	ENST00000797283.1		n.117+11368A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727192

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44720

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

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: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111914

Other (OTH) AF: 0.00 AC: 0 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.11
DANN	Benign	0.44
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0055	N
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.4
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.050
Sift	Benign	0.60	T
Sift4G	Benign	0.71	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.16		Loss of stability (P = 0.019)
MVP		0.030
MPC		0.20
ClinPred		0.041	T
GERP RS		-6.6
PromoterAI		0.0085	Neutral
Varity_R		0.056
gMVP		0.023
Mutation Taster		=100/0	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: rs776584128; hg19: chr21-31859631;