17-41084523-A-C

Variant names:

• chr17-41084523-A-C
• rs760301753
• NM_033061.4:c.317A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033061.4(KRTAP4-7):​c.317A>C​(p.Gln106Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 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. Q106L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0000070 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-7 NM_033061.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998
• Publications: 0 publications found

Genes affected

KRTAP4-7 (HGNC:18898): (keratin associated protein 4-7) 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12439042).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033061.4. 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
	KRTAP4-7	NM_033061.4	MANE Select	c.317A>C	p.Gln106Pro	missense	Exon 1 of 1	NP_149050.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-7	ENST00000391417.6	TSL:6 MANE Select	c.317A>C	p.Gln106Pro	missense	Exon 1 of 1	ENSP00000375236.4	Q9BYR0

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 143226 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 242946 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000701 AC: 10 AN: 1426754 Hom.: 0 Cov.: 135 AF XY: 0.00000846 AC XY: 6 AN XY: 709622

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31874

American (AMR) AF: 0.0000233 AC: 1 AN: 42944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25278

East Asian (EAS) AF: 0.00 AC: 0 AN: 38924

South Asian (SAS) AF: 0.0000238 AC: 2 AN: 83922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5046

European-Non Finnish (NFE) AF: 0.00000552 AC: 6 AN: 1087920

Other (OTH) AF: 0.0000170 AC: 1 AN: 58802

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 143226 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 69708

African (AFR) AF: 0.00 AC: 0 AN: 37852

American (AMR) AF: 0.00 AC: 0 AN: 14380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3358

East Asian (EAS) AF: 0.00 AC: 0 AN: 4974

South Asian (SAS) AF: 0.00 AC: 0 AN: 4460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65306

Other (OTH) AF: 0.00 AC: 0 AN: 1954

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.82
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.91	T
PhyloP100		-1.0
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.11
Sift	Uncertain	0.013	D
Sift4G	Benign	0.14	T
Vest4		0.19
MutPred		0.50		Loss of sheet (P = 0.1158)
MVP		0.076
MPC		0.039
ClinPred		0.24	T
GERP RS		1.1
PromoterAI		0.011	Neutral
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs760301753; hg19: chr17-39240775;