NM_033059.4:c.320C>T

Variant names:

• chr17-41117996-G-A
• rs762322240
• NM_033059.4:c.320C>T

Variant summary

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

The NM_033059.4(KRTAP4-11):​c.320C>T​(p.Ser107Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,480,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: KRTAP4-11 NM_033059.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14597622).

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.320C>T	p.Ser107Phe	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.320C>T	p.Ser107Phe	missense	Exon 1 of 1	ENSP00000375232.2	Q9BYQ6

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 17 AN: 146868 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000400

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000675

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: 0.000495

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 246682 AF XY: 0.00000744

Gnomad AFR exome AF: 0.0000696

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 AF: 0.00000600 AC: 8 AN: 1333546 Hom.: 0 Cov.: 197 AF XY: 0.00000456 AC XY: 3 AN XY: 657204

African (AFR) AF: 0.000104 AC: 3 AN: 28798

American (AMR) AF: 0.00 AC: 0 AN: 38218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23034

East Asian (EAS) AF: 0.00 AC: 0 AN: 35484

South Asian (SAS) AF: 0.00 AC: 0 AN: 67088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4858

European-Non Finnish (NFE) AF: 0.00000193 AC: 2 AN: 1036322

Other (OTH) AF: 0.0000559 AC: 3 AN: 53674

GnomAD4 genome AF: 0.000116 AC: 17 AN: 146964 Hom.: 0 Cov.: 29 AF XY: 0.000125 AC XY: 9 AN XY: 71808

African (AFR) AF: 0.000399 AC: 15 AN: 37564

American (AMR) AF: 0.0000674 AC: 1 AN: 14842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 4910

South Asian (SAS) AF: 0.00 AC: 0 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67700

Other (OTH) AF: 0.000490 AC: 1 AN: 2040

Alfa AF: 0.000285 Hom.: 0

ExAC AF: 0.0000257 AC: 3

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	0.41
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		3.1
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.10
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.45	B
Vest4		0.19
MVP		0.34
MPC		0.0086
ClinPred		0.48	T
GERP RS		4.3
PromoterAI		-0.0014	Neutral
Varity_R		0.14
gMVP		0.062
Mutation Taster		=98/2	polymorphism

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: rs762322240; hg19: chr17-39274248; COSMIC: COSV101194909;