11-1585021-C-G

Position:

• chr11-1585021-C-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001005922.1(KRTAP5-1):​c.229G>C​(p.Gly77Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.490

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 Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28557134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-1	NM_001005922.1	c.229G>C	p.Gly77Arg	missense_variant	1/1	ENST00000382171.2	NP_001005922.1
KRTAP5-AS1	NR_021489.2	n.328+11953C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-1	ENST00000382171.2	c.229G>C	p.Gly77Arg	missense_variant	1/1		NM_001005922.1	ENSP00000371606	P1
KRTAP5-AS1	ENST00000424148.1	n.328+11953C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000138 AC: 2 AN: 1450884 Hom.: 0 Cov.: 51 AF XY: 0.00000139 AC XY: 1 AN XY: 721910

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.229G>C (p.G77R) alteration is located in exon 1 (coding exon 1) of the KRTAP5-1 gene. This alteration results from a G to C substitution at nucleotide position 229, causing the glycine (G) at amino acid position 77 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.075
Eigen_PC	Benign	-0.091
FATHMM_MKL	Benign	0.20	N
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.99	N
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.064	T
Polyphen		1.0	D
Vest4		0.43
MutPred		0.23		Loss of glycosylation at S75 (P = 0.0896);
MVP		0.20
MPC		0.047
ClinPred		0.82	D
GERP RS		2.7
Varity_R		0.25
gMVP		0.064

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

LitVar

Other links and lift over

dbSNP: rs371534043; hg19: chr11-1606251;