15-43603445-C-T

Variant names:

• chr15-43603445-C-T
• rs2260160
• NM_153700.2:c.4376-34G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153700.2(STRC):​c.4376-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,605,710 control chromosomes in the GnomAD database, including 27,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (8290 hom., cov: 31)
  • Exomes 𝑓: 0.13 (19452 hom.)
• Consequence: STRC NM_153700.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.584
• Publications: 19 publications found

Genes affected

STRC (HGNC:16035): (stereocilin) This gene encodes a protein that is associated with the hair bundle of the sensory hair cells in the inner ear. The hair bundle is composed of stiff microvilli called stereocilia and is involved with mechanoreception of sound waves. This gene is part of a tandem duplication on chromosome 15; the second copy is a pseudogene. Mutations in this gene cause autosomal recessive non-syndromic deafness. [provided by RefSeq, Jul 2008]

CKMT1B (HGNC:1995): (creatine kinase, mitochondrial 1B) Mitochondrial creatine (MtCK) kinase is responsible for the transfer of high energy phosphate from mitochondria to the cytosolic carrier, creatine. It belongs to the creatine kinase isoenzyme family. It exists as two isoenzymes, sarcomeric MtCK and ubiquitous MtCK, encoded by separate genes. Mitochondrial creatine kinase occurs in two different oligomeric forms: dimers and octamers, in contrast to the exclusively dimeric cytosolic creatine kinase isoenzymes. Many malignant cancers with poor prognosis have shown overexpression of ubiquitous mitochondrial creatine kinase; this may be related to high energy turnover and failure to eliminate cancer cells via apoptosis. Ubiquitous mitochondrial creatine kinase has 80% homology with the coding exons of sarcomeric mitochondrial creatine kinase. Two genes located near each other on chromosome 15 have been identified which encode identical mitochondrial creatine kinase proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-43603445-C-T is Benign according to our data. Variant chr15-43603445-C-T is described in ClinVar as Benign. ClinVar VariationId is 1275080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153700.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	NM_153700.2	MANE Select	c.4376-34G>A		intron	N/A	NP_714544.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	ENST00000450892.7	TSL:5 MANE Select	c.4376-34G>A		intron	N/A	ENSP00000401513.2
	STRC	ENST00000440125.5	TSL:1	n.*2168-34G>A		intron	N/A	ENSP00000394866.1
	STRC	ENST00000493750.1	TSL:4	n.138G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38268 AN: 151560 Hom.: 8246 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.218

GnomAD2 exomes AF: 0.179 AC: 44337 AN: 247432 AF XY: 0.169

Gnomad AFR exome AF: 0.586

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.191

Gnomad EAS exome AF: 0.333

Gnomad FIN exome AF: 0.0742

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.130 AC: 188328 AN: 1454032 Hom.: 19452 Cov.: 31 AF XY: 0.130 AC XY: 93970 AN XY: 723666

African (AFR) AF: 0.599 AC: 19986 AN: 33384

American (AMR) AF: 0.207 AC: 9269 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4958 AN: 26110

East Asian (EAS) AF: 0.337 AC: 13351 AN: 39658

South Asian (SAS) AF: 0.188 AC: 16163 AN: 86148

European-Finnish (FIN) AF: 0.0737 AC: 3624 AN: 49188

Middle Eastern (MID) AF: 0.149 AC: 855 AN: 5756

European-Non Finnish (NFE) AF: 0.0997 AC: 110561 AN: 1108824

Other (OTH) AF: 0.159 AC: 9561 AN: 60272

GnomAD4 genome AF: 0.253 AC: 38375 AN: 151678 Hom.: 8290 Cov.: 31 AF XY: 0.251 AC XY: 18587 AN XY: 74112

African (AFR) AF: 0.579 AC: 23817 AN: 41162

American (AMR) AF: 0.208 AC: 3177 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 640 AN: 3464

East Asian (EAS) AF: 0.325 AC: 1674 AN: 5154

South Asian (SAS) AF: 0.205 AC: 985 AN: 4804

European-Finnish (FIN) AF: 0.0747 AC: 790 AN: 10570

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.0982 AC: 6676 AN: 67972

Other (OTH) AF: 0.221 AC: 465 AN: 2102

Alfa AF: 0.158 Hom.: 5944

Bravo AF: 0.281

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.28
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs2260160; hg19: chr15-43895643; COSMIC: COSV55853491; COSMIC: COSV55853491;