chr17-41034417-C-G

Variant names:

• chr17-41034417-C-G
• rs201961215
• NM_030966.2:c.405G>C

Variant summary

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

The NM_030966.2(KRTAP1-3):​c.405G>C​(p.Gln135His) 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 1,461,434 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRTAP1-3 NM_030966.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30
• Publications: 0 publications found

Genes affected

KRTAP1-3 (HGNC:16771): (keratin associated protein 1-3) 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: 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_030966.2. 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
	KRTAP1-3	NM_030966.2	MANE Select	c.405G>C	p.Gln135His	missense	Exon 1 of 1	NP_112228.1	Q8IUG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP1-3	ENST00000344363.7	TSL:6 MANE Select	c.405G>C	p.Gln135His	missense	Exon 1 of 1	ENSP00000344420.5	Q8IUG1
	ENSG00000306126	ENST00000815517.1		n.220-25882C>G		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-25882C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461434 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726998

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5630

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.63	T
PhyloP100		2.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.26
Sift	Uncertain	0.016	D
Sift4G	Benign	0.11	T
Vest4		0.58
MVP		0.27
MPC		0.41
ClinPred		0.98	D
GERP RS		4.5
PromoterAI		-0.015	Neutral
gMVP		0.19

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

Other links and lift over

dbSNP: rs201961215; hg19: chr17-39190669;