chr4-182346812-A-T

Variant names:

• chr4-182346812-A-T
• NM_001080477.4:c.394A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080477.4(TENM3):​c.394A>T​(p.Met132Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TENM3 NM_001080477.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23462543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.394A>T	p.Met132Leu	missense_variant	Exon 3 of 28	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.394A>T	p.Met132Leu	missense_variant	Exon 3 of 28	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000513201.1	n.644A>T		non_coding_transcript_exon_variant	Exon 3 of 4	1
TENM3	ENST00000512480.5	c.394A>T	p.Met132Leu	missense_variant	Exon 3 of 3	3		ENSP00000421320.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461354 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726904

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.68
DEOGEN2	Benign	0.044	.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.089
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	.;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.021	B;B
Vest4		0.51
MutPred		0.39		Gain of glycosylation at S127 (P = 0.0938);Gain of glycosylation at S127 (P = 0.0938);
MVP		0.20
MPC		0.27
ClinPred		0.60	D
GERP RS		4.9
Varity_R		0.16
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-183267965;