11-1584580-C-G

Variant names:

• chr11-1584580-C-G
• rs760830486
• NM_001005922.1:c.670G>C

Variant summary

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

The NM_001005922.1(KRTAP5-1):​c.670G>C​(p.Ala224Pro) 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. 15/21 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. A224E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.15
• Publications: 0 publications found

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

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=0.06970191).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005922.1. 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
	KRTAP5-1	NM_001005922.1	MANE Select	c.670G>C	p.Ala224Pro	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11512C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-1	ENST00000382171.2	TSL:6 MANE Select	c.670G>C	p.Ala224Pro	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11512C>G		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12668C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.0
DANN	Benign	0.53
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0063	N
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
PhyloP100		-4.1
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.058
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.22	T
Polyphen		0.75	P
Vest4		0.17
MutPred		0.18		Gain of glycosylation at A224 (P = 0.0685)
MVP		0.13
MPC		0.049
ClinPred		0.14	T
GERP RS		0.40
Varity_R		0.090
gMVP		0.013
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs760830486; hg19: chr11-1605810;