11-1597982-G-A

Variant names:

• chr11-1597982-G-A
• rs1258475561
• NM_001004325.2:c.269C>T

Variant summary

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

The NM_001004325.2(KRTAP5-2):​c.269C>T​(p.Ser90Phe) 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. 14/21 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. S90Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: KRTAP5-2 NM_001004325.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 0 publications found

Genes affected

KRTAP5-2 (HGNC:23597): (keratin associated protein 5-2) 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=0.21836224).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004325.2. 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
	KRTAP5-2	NM_001004325.2	MANE Select	c.269C>T	p.Ser90Phe	missense	Exon 1 of 1	NP_001004325.1	Q701N4
	KRTAP5-AS1	NR_021489.2		n.1063G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-2	ENST00000412090.2	TSL:6 MANE Select	c.269C>T	p.Ser90Phe	missense	Exon 1 of 1	ENSP00000400041.1	Q701N4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.1063G>A		non_coding_transcript_exon	Exon 2 of 2
	KRTAP5-AS1	ENST00000792906.1		n.214-14383G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
PhyloP100		-0.49
PromoterAI		0.0030	Neutral
Varity_R		0.25
gMVP		0.036
Mutation Taster		=95/5	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: rs1258475561; hg19: chr11-1619212; COSMIC: COSV69015029; COSMIC: COSV69015029;