4-182346575-TAAA-TAAAA

Variant names:

• chr4-182346575-T-TA
• rs33933747
• NM_001080477.4:c.233-62dupA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001080477.4(TENM3):​c.233-62dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 874,976 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 0.000027 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

Genes affected

TENM3 (HGNC:29944): (teneurin transmembrane protein 3) This gene encodes a member of the teneurin transmembrane protein family. The encoded protein may be involved in the regulation of neuronal development including development of the visual pathway. Mutations in this gene have been associated with microphthalmia and developmental dysplasia of the hip. [provided by RefSeq, Jan 2023]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00153 (1115/728556) while in subpopulation AFR AF= 0.00756 (137/18112). AF 95% confidence interval is 0.00653. There are 0 homozygotes in gnomad4_exome. There are 577 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.233-62dupA		intron_variant	Intron 2 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.233-76_233-75insA		intron_variant	Intron 2 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000513201.1	n.483-76_483-75insA		intron_variant	Intron 2 of 3	1
TENM3	ENST00000512480.5	c.233-76_233-75insA		intron_variant	Intron 2 of 2	3		ENSP00000421320.1

Frequencies

GnomAD3 genomes AF: 0.0000273 AC: 4 AN: 146420 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000501

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: 0.0000300

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00153 AC: 1115 AN: 728556 Hom.: 0 AF XY: 0.00158 AC XY: 577 AN XY: 364148

Gnomad4 AFR exome AF: 0.00756

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00387

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00286

Gnomad4 FIN exome AF: 0.000421

Gnomad4 NFE exome AF: 0.00131

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.0000273 AC: 4 AN: 146420 Hom.: 0 Cov.: 0 AF XY: 0.0000282 AC XY: 2 AN XY: 71034

Gnomad4 AFR AF: 0.0000501

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: 0.0000300

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs33933747; hg19: chr4-183267728;