NM_181612.3:c.55G>C

Variant names:

• chr21-30541779-C-G
• rs1978780528
• NM_181612.3:c.55G>C

Variant summary

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

The NM_181612.3(KRTAP19-6):​c.55G>C​(p.Gly19Arg) 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. 13/20 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: KRTAP19-6 NM_181612.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.545
• Publications: 0 publications found

Genes affected

KRTAP19-6 (HGNC:18941): (keratin associated protein 19-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000308278 (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=0.08847594).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181612.3. 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
	KRTAP19-6	NM_181612.3	MANE Select	c.55G>C	p.Gly19Arg	missense	Exon 1 of 1	NP_853643.1	Q3LI70

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP19-6	ENST00000334046.5	TSL:6 MANE Select	c.55G>C	p.Gly19Arg	missense	Exon 1 of 1	ENSP00000375107.3	Q3LI70
	ENSG00000308278	ENST00000832954.1		n.124+10816C>G		intron	N/A
	ENSG00000308278	ENST00000832955.1		n.165+10816C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.9
DANN	Benign	0.39
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.55
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.043
Sift4G	Benign	0.10	T
Polyphen		0.41	B
Vest4		0.26
MutPred		0.26		Gain of methylation at G19 (P = 0.0071)
MVP		0.055
MPC		0.28
ClinPred		0.21	T
GERP RS		-5.9
PromoterAI		0.019	Neutral
Varity_R		0.32
gMVP		0.076
Mutation Taster		=99/1	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: rs1978780528; hg19: chr21-31914098;