KRTAP1-5 p.Thr173Ser

Variant names:

• chr17-41026639-T-A
• NM_031957.2:c.517A>T
• KRTAP1-5 p.Thr173Ser

Your query was ambiguous. Multiple possible variants found:

• chr17-41026639-T-A
• chr17-41026638-G-C
• chr17-41026637-AGT-GGA
• chr17-41026637-AGT-TGA
• chr17-41026637-AGT-CGA
• chr17-41026637-AG-GC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031957.2(KRTAP1-5):​c.517A>T​(p.Thr173Ser) 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. 16/22 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. T173I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP1-5 NM_031957.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 0 publications found

Genes affected

KRTAP1-5 (HGNC:16777): (keratin associated protein 1-5) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the high sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

ENSG00000306126 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051469624).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031957.2. 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
	KRTAP1-5	NM_031957.2	MANE Select	c.517A>T	p.Thr173Ser	missense	Exon 1 of 1	NP_114163.1	Q9BYS1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP1-5	ENST00000361883.6	TSL:6 MANE Select	c.517A>T	p.Thr173Ser	missense	Exon 1 of 1	ENSP00000355302.5	Q9BYS1
	ENSG00000306126	ENST00000815517.1		n.220-33660T>A		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-33660T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.70
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.31	N
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.26
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.061
Sift	Benign	0.20	T
Sift4G	Benign	0.57	T
Varity_R		0.038
gMVP		0.075

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

hg19: chr17-39182891;