rs2014065127

Variant names:

• chr17-41105458-T-A
• rs2014065127
• NM_001146041.1:c.70T>A

Your query was ambiguous. Multiple possible variants found:

• chr17-41105458-T-A
• chr17-41105458-T-G

Variant summary

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

The NM_001146041.1(KRTAP4-9):​c.70T>A​(p.Cys24Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,164 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. C24G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRTAP4-9 NM_001146041.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.70T>A	p.Cys24Ser	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.70T>A	p.Cys24Ser	missense	Exon 1 of 1	ENSP00000375234.1	Q9BYQ8

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459164 Hom.: 0 Cov.: 135 AF XY: 0.00 AC XY: 0 AN XY: 725928

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109646

Other (OTH) AF: 0.00 AC: 0 AN: 60286

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		1.5
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Uncertain	0.31
Sift	Benign	0.040	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.18
MutPred		0.64		Gain of relative solvent accessibility (P = 0.0104)
MVP		0.47
MPC		0.22
ClinPred		0.88	D
GERP RS		3.3
PromoterAI		-0.0054	Neutral
Varity_R		0.59
gMVP		0.080

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2014065127; hg19: chr17-39261710;