17-41105797-C-A

Variant names:

• chr17-41105797-C-A
• rs779680132
• NM_001146041.1:c.409C>A

Variant summary

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

The NM_001146041.1(KRTAP4-9):​c.409C>A​(p.Pro137Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P137A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KRTAP4-9 NM_001146041.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 0 publications found

Genes affected

KRTAP4-9 (HGNC:18910): (keratin associated protein 4-9) Involved in aging and hair cycle. 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=0.2151809).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146041.1. 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
	KRTAP4-9	NM_001146041.1	MANE Select	c.409C>A	p.Pro137Thr	missense	Exon 1 of 1	NP_001139513.1	Q9BYQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-9	ENST00000391415.2	TSL:6 MANE Select	c.409C>A	p.Pro137Thr	missense	Exon 1 of 1	ENSP00000375234.1	Q9BYQ8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459376 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 725986

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 44356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 86006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110802

Other (OTH) AF: 0.00 AC: 0 AN: 60266

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.28
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Benign	0.089
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.010	D
Polyphen		0.95	P
Vest4		0.27
MutPred		0.50		Loss of loop (P = 0.0804)
MVP		0.15
MPC		0.20
ClinPred		0.35	T
GERP RS		2.6
PromoterAI		-0.0054	Neutral
Varity_R		0.17
gMVP		0.067
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs779680132; hg19: chr17-39262049;