rs531605465

Variant names:

• chr17-41105774-G-A
• NM_001146041.1:c.386G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-41105774-G-A
• chr17-41105774-G-C
• chr17-41105774-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146041.1(KRTAP4-9):​c.386G>A​(p.Cys129Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,132 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. C129F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KRTAP4-9 NM_001146041.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20303845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-9	NM_001146041.1	c.386G>A	p.Cys129Tyr	missense_variant	Exon 1 of 1	ENST00000391415.2	NP_001139513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-9	ENST00000391415.2	c.386G>A	p.Cys129Tyr	missense_variant	Exon 1 of 1	6	NM_001146041.1	ENSP00000375234.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451132 Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1 AN XY: 721440

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.80
DEOGEN2	Benign	0.066	T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.5	H;.
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-8.9	D;.
REVEL	Benign	0.12
Sift	Uncertain	0.0080	D;.
Sift4G	Uncertain	0.019	D;D
Polyphen		0.058	B;.
Vest4		0.16
MutPred		0.47		Gain of sheet (P = 0.1208);.;
MVP		0.18
MPC		0.30
ClinPred		0.29	T
GERP RS		2.1
Varity_R		0.59
gMVP		0.066

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39262026;