NM_032524.2:c.267A>G

Variant names:

• chr17-41160425-T-C
• rs201753814
• NM_032524.2:c.267A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_032524.2(KRTAP4-4):​c.267A>G​(p.Gln89Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000346 in 1,389,018 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000043 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: KRTAP4-4 NM_032524.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.762
• Publications: 2 publications found

Genes affected

KRTAP4-4 (HGNC:16928): (keratin associated protein 4-4) 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, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-41160425-T-C is Benign according to our data. Variant chr17-41160425-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2647761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.762 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032524.2. 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
	KRTAP4-4	NM_032524.2	MANE Select	c.267A>G	p.Gln89Gln	synonymous	Exon 1 of 1	NP_115913.1	Q9BYR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-4	ENST00000390661.5	TSL:6 MANE Select	c.267A>G	p.Gln89Gln	synonymous	Exon 1 of 1	ENSP00000375076.3	Q9BYR3

Frequencies

GnomAD3 genomes AF: 0.0000433 AC: 3 AN: 69210 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: 0.0000896

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000302 AC: 7 AN: 232066 AF XY: 0.0000316

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: 0.0000561

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000341 AC: 45 AN: 1319808 Hom.: 0 Cov.: 32 AF XY: 0.0000411 AC XY: 27 AN XY: 656242

African (AFR) AF: 0.00 AC: 0 AN: 28148

American (AMR) AF: 0.00 AC: 0 AN: 35734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20990

East Asian (EAS) AF: 0.00 AC: 0 AN: 28044

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4994

European-Non Finnish (NFE) AF: 0.0000419 AC: 43 AN: 1026822

Other (OTH) AF: 0.0000195 AC: 1 AN: 51192

GnomAD4 genome AF: 0.0000433 AC: 3 AN: 69210 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33752

African (AFR) AF: 0.00 AC: 0 AN: 17624

American (AMR) AF: 0.00 AC: 0 AN: 6940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1780

East Asian (EAS) AF: 0.00 AC: 0 AN: 2160

South Asian (SAS) AF: 0.00 AC: 0 AN: 1976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 68

European-Non Finnish (NFE) AF: 0.0000896 AC: 3 AN: 33474

Other (OTH) AF: 0.00 AC: 0 AN: 992

Alfa AF: 0.0000627 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.31
PhyloP100		-0.76
PromoterAI		-0.0070	Neutral

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: rs201753814; hg19: chr17-39316677; COSMIC: COSV101180573;