rs3745510

Variant names:

• chr19-50293703-C-T
• rs3745510
• NM_001145809.2:c.5469+16C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-50293703-C-T
• chr19-50293703-C-A
• chr19-50293703-C-G

Variant summary

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

The NM_001145809.2(MYH14):​c.5469+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,542,138 control chromosomes in the GnomAD database, including 424,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (35484 hom., cov: 33)
  • Exomes 𝑓: 0.74 (389189 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -4.41
• Publications: 10 publications found

Genes affected

MYH14 (HGNC:23212): (myosin heavy chain 14) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MYH14 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 4A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-50293703-C-T is Benign according to our data. Variant chr19-50293703-C-T is described in ClinVar as Benign. ClinVar VariationId is 257578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145809.2. 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
	MYH14	NM_001145809.2	MANE Select	c.5469+16C>T		intron	N/A	NP_001139281.1	Q7Z406-2
	MYH14	NM_001077186.2		c.5370+16C>T		intron	N/A	NP_001070654.1	Q7Z406-6
	MYH14	NM_024729.4		c.5346+16C>T		intron	N/A	NP_079005.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000642316.2	MANE Select	c.5469+16C>T		intron	N/A	ENSP00000493594.1	Q7Z406-2
	MYH14	ENST00000425460.6	TSL:5	c.5370+16C>T		intron	N/A	ENSP00000407879.1	Q7Z406-6
	MYH14	ENST00000598205.5	TSL:5	c.5370+16C>T		intron	N/A	ENSP00000472543.1	Q7Z406-6

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100501 AN: 152014 Hom.: 35464 Cov.: 33

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.685

GnomAD2 exomes AF: 0.754 AC: 149415 AN: 198216 AF XY: 0.757

Gnomad AFR exome AF: 0.388

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.711

Gnomad EAS exome AF: 0.931

Gnomad FIN exome AF: 0.768

Gnomad NFE exome AF: 0.747

Gnomad OTH exome AF: 0.747

GnomAD4 exome AF: 0.745 AC: 1035465 AN: 1390006 Hom.: 389189 Cov.: 41 AF XY: 0.746 AC XY: 509743 AN XY: 683016

African (AFR) AF: 0.384 AC: 12159 AN: 31626

American (AMR) AF: 0.846 AC: 29639 AN: 35030

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 15314 AN: 21474

East Asian (EAS) AF: 0.910 AC: 35425 AN: 38948

South Asian (SAS) AF: 0.785 AC: 58582 AN: 74664

European-Finnish (FIN) AF: 0.766 AC: 38954 AN: 50878

Middle Eastern (MID) AF: 0.731 AC: 3909 AN: 5348

European-Non Finnish (NFE) AF: 0.744 AC: 799947 AN: 1074786

Other (OTH) AF: 0.725 AC: 41536 AN: 57252

GnomAD4 genome AF: 0.661 AC: 100560 AN: 152132 Hom.: 35484 Cov.: 33 AF XY: 0.669 AC XY: 49765 AN XY: 74368

African (AFR) AF: 0.394 AC: 16345 AN: 41468

American (AMR) AF: 0.774 AC: 11827 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2507 AN: 3472

East Asian (EAS) AF: 0.923 AC: 4782 AN: 5182

South Asian (SAS) AF: 0.779 AC: 3760 AN: 4824

European-Finnish (FIN) AF: 0.764 AC: 8085 AN: 10584

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 51004 AN: 68000

Other (OTH) AF: 0.688 AC: 1451 AN: 2110

Alfa AF: 0.722 Hom.: 19153

Bravo AF: 0.651

Asia WGS AF: 0.838 AC: 2912 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Autosomal dominant nonsyndromic hearing loss 4A (1)
-	-	1	Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.034
DANN	Benign	0.52
PhyloP100		-4.4
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: rs3745510; hg19: chr19-50796960;