17-41118015-G-C

Variant names:

• chr17-41118015-G-C
• rs754668043
• NM_033059.4:c.301C>G

Variant summary

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

The NM_033059.4(KRTAP4-11):​c.301C>G​(p.Arg101Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000752 in 1,329,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R101H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: KRTAP4-11 NM_033059.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.00
• Publications: 0 publications found

Genes affected

KRTAP4-11 (HGNC:18911): (keratin associated protein 4-11) 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 ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Mar 2009]

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=0.07507813).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033059.4. 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
	KRTAP4-11	NM_033059.4	MANE Select	c.301C>G	p.Arg101Gly	missense	Exon 1 of 1	NP_149048.2	Q9BYQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-11	ENST00000391413.4	TSL:6 MANE Select	c.301C>G	p.Arg101Gly	missense	Exon 1 of 1	ENSP00000375232.2	Q9BYQ6

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1329088 Hom.: 0 Cov.: 198 AF XY: 0.00 AC XY: 0 AN XY: 654734

African (AFR) AF: 0.00 AC: 0 AN: 28688

American (AMR) AF: 0.00 AC: 0 AN: 37866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22854

East Asian (EAS) AF: 0.00 AC: 0 AN: 35320

South Asian (SAS) AF: 0.00 AC: 0 AN: 66280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4832

European-Non Finnish (NFE) AF: 9.67e-7 AC: 1 AN: 1033936

Other (OTH) AF: 0.00 AC: 0 AN: 53476

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.3
DANN	Benign	0.56
DEOGEN2	Benign	0.088	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-8.0
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.13
Sift	Benign	0.092	T
Sift4G	Benign	0.15	T
Polyphen		0.14	B
Vest4		0.074
MutPred		0.48		Gain of catalytic residue at R101 (P = 0.0811)
MVP		0.085
MPC		0.0083
ClinPred		0.69	D
GERP RS		-7.9
PromoterAI		-0.0010	Neutral
Varity_R		0.25
gMVP		0.075
Mutation Taster		=100/0	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: rs754668043; hg19: chr17-39274267;