rs2729509

Variant names:

• chr15-43618242-A-G
• rs2729509
• NM_153700.2:c.179T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-43618242-A-G
• chr15-43618242-A-C
• chr15-43618242-A-T

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.179T>C​(p.Phe60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (6309 hom., cov: 11)
  • Exomes 𝑓: 0.30 (26224 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9 O:1
• Conservation: PhyloP100: 3.27
• Publications: 11 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]

STRC Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 16

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000284772 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=3.956515E-5).
• BP6: Variant 15-43618242-A-G is Benign according to our data. Variant chr15-43618242-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 156030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	NM_153700.2	MANE Select	c.179T>C	p.Phe60Ser	missense	Exon 2 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.179T>C	p.Phe60Ser	missense	Exon 2 of 29	ENSP00000401513.2	Q7RTU9
	STRC	ENST00000440125.5	TSL:1	n.179T>C		non_coding_transcript_exon	Exon 2 of 28	ENSP00000394866.1	E7EPM8
	ENSG00000284772	ENST00000643290.1		n.*342T>C		non_coding_transcript_exon	Exon 4 of 9	ENSP00000495476.1	A0A2R8Y6Q2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 30410 AN: 88536 Hom.: 6287 Cov.: 11

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.428

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.354

GnomAD2 exomes AF: 0.345 AC: 23061 AN: 66768 AF XY: 0.341

Gnomad AFR exome AF: 0.680

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.336

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.301 AC: 167071 AN: 555480 Hom.: 26224 Cov.: 7 AF XY: 0.303 AC XY: 88794 AN XY: 293154

African (AFR) AF: 0.672 AC: 9787 AN: 14554

American (AMR) AF: 0.313 AC: 9027 AN: 28848

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 6393 AN: 16754

East Asian (EAS) AF: 0.329 AC: 10433 AN: 31686

South Asian (SAS) AF: 0.369 AC: 19795 AN: 53580

European-Finnish (FIN) AF: 0.185 AC: 5668 AN: 30684

Middle Eastern (MID) AF: 0.400 AC: 917 AN: 2290

European-Non Finnish (NFE) AF: 0.275 AC: 95341 AN: 347232

Other (OTH) AF: 0.325 AC: 9710 AN: 29852

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.344 AC: 30462 AN: 88600 Hom.: 6309 Cov.: 11 AF XY: 0.340 AC XY: 13940 AN XY: 41038

African (AFR) AF: 0.638 AC: 11567 AN: 18134

American (AMR) AF: 0.321 AC: 2867 AN: 8924

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 915 AN: 2564

East Asian (EAS) AF: 0.310 AC: 995 AN: 3210

South Asian (SAS) AF: 0.340 AC: 704 AN: 2068

European-Finnish (FIN) AF: 0.169 AC: 1130 AN: 6704

Middle Eastern (MID) AF: 0.441 AC: 112 AN: 254

European-Non Finnish (NFE) AF: 0.259 AC: 11660 AN: 45026

Other (OTH) AF: 0.356 AC: 389 AN: 1092

Alfa AF: 0.187 Hom.: 456

ExAC AF: 0.197 AC: 2282

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Autosomal recessive nonsyndromic hearing loss 16 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.54
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.000040	T
MetaSVM	Benign	-0.92	T
PhyloP100		3.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	0.63	T
Polyphen		0.0	B
Vest4		0.26
ClinPred		0.0030	T
GERP RS		3.4
PromoterAI		-0.0031	Neutral
Varity_R		0.043
gMVP		0.21
Mutation Taster		=99/1	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: rs2729509; hg19: chr15-43910440; COSMIC: COSV70833187; COSMIC: COSV70833187;