NM_153700.2:c.5200T>C

Variant names:

• chr15-43599999-A-G
• rs200770543
• NM_153700.2:c.5200T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_153700.2(STRC):​c.5200T>C​(p.Trp1734Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,440,188 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 21)
  • Exomes 𝑓: 0.0017 (22 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.10
• Publications: 0 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014477223).
• BP6: Variant 15-43599999-A-G is Benign according to our data. Variant chr15-43599999-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 505196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 22 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	NM_153700.2	MANE Select	c.5200T>C	p.Trp1734Arg	missense	Exon 28 of 29	NP_714544.1	Q7RTU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	ENST00000450892.7	TSL:5 MANE Select	c.5200T>C	p.Trp1734Arg	missense	Exon 28 of 29	ENSP00000401513.2	Q7RTU9
	STRC	ENST00000440125.5	TSL:1	n.*2992T>C		non_coding_transcript_exon	Exon 27 of 28	ENSP00000394866.1	E7EPM8
	STRC	ENST00000440125.5	TSL:1	n.*2992T>C		3_prime_UTR	Exon 27 of 28	ENSP00000394866.1	E7EPM8

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 171 AN: 143872 Hom.: 1 Cov.: 21

Gnomad AFR AF: 0.00122

Gnomad AMI AF: 0.0145

Gnomad AMR AF: 0.000422

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: 0.00158

Gnomad OTH AF: 0.000517

GnomAD2 exomes AF: 0.000955 AC: 192 AN: 201040 AF XY: 0.000922

Gnomad AFR exome AF: 0.00153

Gnomad AMR exome AF: 0.000586

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000559

Gnomad NFE exome AF: 0.00171

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00168 AC: 2424 AN: 1440188 Hom.: 22 Cov.: 29 AF XY: 0.00167 AC XY: 1200 AN XY: 716502

African (AFR) AF: 0.000785 AC: 26 AN: 33114

American (AMR) AF: 0.000456 AC: 20 AN: 43896

Ashkenazi Jewish (ASJ) AF: 0.0000774 AC: 2 AN: 25836

East Asian (EAS) AF: 0.00 AC: 0 AN: 39528

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84090

European-Finnish (FIN) AF: 0.0000565 AC: 3 AN: 53098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00212 AC: 2322 AN: 1095204

Other (OTH) AF: 0.000838 AC: 50 AN: 59696

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00119 AC: 171 AN: 143980 Hom.: 1 Cov.: 21 AF XY: 0.00116 AC XY: 81 AN XY: 69778

African (AFR) AF: 0.00122 AC: 47 AN: 38670

American (AMR) AF: 0.000422 AC: 6 AN: 14230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3378

East Asian (EAS) AF: 0.00 AC: 0 AN: 4776

South Asian (SAS) AF: 0.00 AC: 0 AN: 4256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00158 AC: 104 AN: 65804

Other (OTH) AF: 0.000512 AC: 1 AN: 1954

Alfa AF: 0.00109 Hom.: 0

Bravo AF: 0.00129

ESP6500AA AF: 0.000914 AC: 4

ESP6500EA AF: 0.00117 AC: 10

ExAC AF: 0.000769 AC: 93

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Autosomal recessive nonsyndromic hearing loss 16 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.91	T
PhyloP100		2.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.23
Sift	Benign	0.055	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.10	B
Vest4		0.60
MutPred		0.35		Loss of helix (P = 0.0104)
MVP		0.66
ClinPred		0.012	T
GERP RS		2.4
Varity_R		0.18
gMVP		0.69
Mutation Taster		=92/8	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: rs200770543; hg19: chr15-43892197;