3-108383733-T-TAAAAACA

Variant names:

• chr3-108383733-T-TAAAAACA
• rs377049870
• NM_014981.3:c.5632-5_5632-4insTGTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014981.3(MYH15):​c.5632-5_5632-4insTGTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000966 in 1,035,004 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 29)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH15 NM_014981.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

Genes affected

MYH15 (HGNC:31073): (myosin heavy chain 15) Predicted to enable several functions, including ATP binding activity; actin filament binding activity; and calmodulin binding activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LOC124900545 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH15	NM_014981.3	c.5632-5_5632-4insTGTTTTT		splice_region_variant, intron_variant	Intron 39 of 40	ENST00000693548.1	NP_055796.2
MYH15	XM_011512559.3	c.5692-5_5692-4insTGTTTTT		splice_region_variant, intron_variant	Intron 41 of 42		XP_011510861.1
LOC124900545	XR_007095998.1	n.112+2087_112+2088insCAAAAAA		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH15	ENST00000693548.1	c.5632-5_5632-4insTGTTTTT		splice_region_variant, intron_variant	Intron 39 of 40		NM_014981.3	ENSP00000508967.1
MYH15	ENST00000273353.5	c.5632-5_5632-4insTGTTTTT		splice_region_variant, intron_variant	Intron 40 of 41	1		ENSP00000273353.4
MYH15	ENST00000689784.1	c.4651-5_4651-4insTGTTTTT		splice_region_variant, intron_variant	Intron 31 of 32			ENSP00000509841.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 59482 Hom.: 0 Cov.: 29 FAILED QC

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.66e-7 AC: 1 AN: 1035004 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 507064

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 59482 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 28054

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs377049870; hg19: chr3-108102580;