NM_181608.2:c.135A>C

Variant names:

• chr21-30487214-T-G
• NM_181608.2:c.135A>C

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.135A>C​(p.Arg45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: KRTAP19-2 NM_181608.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.721
• 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=0.041511536).

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.135A>C	p.Arg45Ser	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.135A>C	p.Arg45Ser	missense	Exon 1 of 1	ENSP00000335660.3	Q3LHN2
	ENSG00000303806	ENST00000797282.1		n.117+11270T>G		intron	N/A
	ENSG00000303806	ENST00000797283.1		n.117+11270T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.099
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.4
DANN	Benign	0.67
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.026	N
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.72
PROVEAN	Benign	0.67	N
REVEL	Benign	0.039
Sift	Benign	0.29	T
Sift4G	Benign	0.096	T
Polyphen		0.017	B
Vest4		0.14
MutPred		0.17		Loss of methylation at R45 (P = 0.0265)
MVP		0.11
MPC		0.18
ClinPred		0.21	T
GERP RS		-0.98
PromoterAI		0.0014	Neutral
Varity_R		0.18
gMVP		0.067
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

hg19: chr21-31859533;