NM_021046.3:c.560T>G

Variant names:

• chr11-71538615-T-G
• rs765031409
• NM_021046.3:c.560T>G

Variant summary

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

The NM_021046.3(KRTAP5-8):​c.560T>G​(p.Ile187Ser) 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. 13/21 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. I187T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRTAP5-8 NM_021046.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 0 publications found

Genes affected

KRTAP5-8 (HGNC:23603): (keratin associated protein 5-8) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07286519).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021046.3. 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
	KRTAP5-8	NM_021046.3	MANE Select	c.560T>G	p.Ile187Ser	missense	Exon 1 of 1	NP_066384.2	O75690

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-8	ENST00000398534.4	TSL:6 MANE Select	c.560T>G	p.Ile187Ser	missense	Exon 1 of 1	ENSP00000420723.1	O75690

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
PhyloP100		-0.19
Varity_R		0.15
gMVP		0.14
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs765031409; hg19: chr11-71249661;