NM_033061.4:c.172G>C

Variant names:

• chr17-41084378-G-C
• rs1268135101
• NM_033061.4:c.172G>C

Variant summary

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

The NM_033061.4(KRTAP4-7):​c.172G>C​(p.Val58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000782 in 1,279,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: KRTAP4-7 NM_033061.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.24
• 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: 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=0.08566514).

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.172G>C	p.Val58Leu	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.172G>C	p.Val58Leu	missense	Exon 1 of 1	ENSP00000375236.4	Q9BYR0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.82e-7 AC: 1 AN: 1279252 Hom.: 0 Cov.: 161 AF XY: 0.00 AC XY: 0 AN XY: 636112

African (AFR) AF: 0.00 AC: 0 AN: 25934

American (AMR) AF: 0.00 AC: 0 AN: 36330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20472

East Asian (EAS) AF: 0.00 AC: 0 AN: 32522

South Asian (SAS) AF: 0.00 AC: 0 AN: 74972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4906

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 985212

Other (OTH) AF: 0.00 AC: 0 AN: 50728

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.54
DANN	Benign	0.74
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.91	T
PhyloP100		-4.2
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.022
Sift	Benign	0.17	T
Sift4G	Benign	0.35	T
Vest4		0.095
MutPred		0.26		Loss of sheet (P = 0.0228)
MVP		0.088
MPC		0.034
ClinPred		0.071	T
GERP RS		-4.4
PromoterAI		0.0081	Neutral
gMVP		0.078
Mutation Taster		=96/4	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: rs1268135101; hg19: chr17-39240630;