11-1584652-C-G

Variant names:

• chr11-1584652-C-G
• NM_001005922.1:c.598G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005922.1(KRTAP5-1):​c.598G>C​(p.Gly200Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,768 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. 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. G200S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

Genes affected

KRTAP5-1 (HGNC:23596): (keratin associated protein 5-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-AS1 (HGNC:27877): (KRTAP5-1/KRTAP5-2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11163759).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-1	NM_001005922.1	c.598G>C	p.Gly200Arg	missense_variant	Exon 1 of 1	ENST00000382171.2	NP_001005922.1
KRTAP5-AS1	NR_021489.2	n.328+11584C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-1	ENST00000382171.2	c.598G>C	p.Gly200Arg	missense_variant	Exon 1 of 1	6	NM_001005922.1	ENSP00000371606.2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445768 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 719126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.59
DANN	Benign	0.53
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00083	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PROVEAN	Benign	0.13	N
REVEL	Benign	0.060
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.21	T
Polyphen		0.92	P
Vest4		0.20
MutPred		0.20		Loss of glycosylation at S199 (P = 0.0379);
MVP		0.076
MPC		0.047
ClinPred		0.14	T
GERP RS		-5.4
Varity_R		0.098
gMVP		0.014

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-1605882;