NM_001123387.1:c.7G>C

Variant names:

• chr17-41047261-C-G
• rs1233820650
• NM_001123387.1:c.7G>C

Variant summary

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

The NM_001123387.1(KRTAP2-1):​c.7G>C​(p.Gly3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,282,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: KRTAP2-1 NM_001123387.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0570
• Publications: 0 publications found

Genes affected

KRTAP2-1 (HGNC:16775): (keratin associated protein 2-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000306126 (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=0.13581309).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123387.1. 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
	KRTAP2-1	NM_001123387.1	MANE Select	c.7G>C	p.Gly3Arg	missense	Exon 1 of 1	NP_001116859.1	Q9BYU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP2-1	ENST00000391419.3	TSL:6 MANE Select	c.7G>C	p.Gly3Arg	missense	Exon 1 of 1	ENSP00000375238.3	Q9BYU5
	ENSG00000306126	ENST00000815517.1		n.220-13038C>G		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-13038C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000312 AC: 4 AN: 1282370 Hom.: 0 Cov.: 30 AF XY: 0.00000320 AC XY: 2 AN XY: 624860

African (AFR) AF: 0.00 AC: 0 AN: 27386

American (AMR) AF: 0.00 AC: 0 AN: 20896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18996

East Asian (EAS) AF: 0.00 AC: 0 AN: 34846

South Asian (SAS) AF: 0.00 AC: 0 AN: 62830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3608

European-Non Finnish (NFE) AF: 0.00000389 AC: 4 AN: 1029026

Other (OTH) AF: 0.00 AC: 0 AN: 53266

GnomAD4 genome Cov.: 30

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	0.27
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.057
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.016	D
Polyphen		0.0090	B
Vest4		0.094
MutPred		0.55		Loss of glycosylation at S4 (P = 0.0478)
MVP		0.20
ClinPred		0.50	T
GERP RS		3.4
PromoterAI		-0.031	Neutral
Varity_R		0.072
gMVP		0.042
Mutation Taster		=97/3	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: rs1233820650; hg19: chr17-39203513;