chr21-30598844-C-G

Variant names:

• chr21-30598844-C-G
• rs533416500
• NM_181604.2:c.31G>C

Variant summary

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

The NM_181604.2(KRTAP6-2):​c.31G>C​(p.Gly11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G11D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRTAP6-2 NM_181604.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• Publications: 0 publications found

Genes affected

KRTAP6-2 (HGNC:18932): (keratin associated protein 6-2) Enables identical protein binding activity. Predicted to be involved in keratinization. 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181604.2. 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
	KRTAP6-2	NM_181604.2	MANE Select	c.31G>C	p.Gly11Arg	missense	Exon 1 of 1	NP_853635.1	Q3LI66

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP6-2	ENST00000334897.4	TSL:6 MANE Select	c.31G>C	p.Gly11Arg	missense	Exon 1 of 1	ENSP00000334560.3	Q3LI66
	ENSG00000308278	ENST00000832954.1		n.176-20985C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461762 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111910

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	19
DANN	Benign	0.80
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.1	T
PhyloP100		3.0
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.19
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.24		Loss of sheet (P = 0.0817)
MVP		0.17
MPC		0.074
ClinPred		0.95	D
GERP RS		3.5
PromoterAI		-0.039	Neutral
Varity_R		0.48
gMVP		0.11
Mutation Taster		=98/2	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: rs533416500; hg19: chr21-31971163;