rs568794165

Variant names:

• chr6-52509560-G-A
• NM_012288.4:c.438C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-52509560-G-A
• chr6-52509560-G-C
• chr6-52509560-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_012288.4(TRAM2):​c.438C>T​(p.Ser146Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TRAM2 NM_012288.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

Genes affected

TRAM2 (HGNC:16855): (translocation associated membrane protein 2) TRAM2 is a component of the translocon, a gated macromolecular channel that controls the posttranslational processing of nascent secretory and membrane proteins at the endoplasmic reticulum (ER) membrane.[supplied by OMIM, Jul 2004]

EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=2.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAM2	NM_012288.4	c.438C>T	p.Ser146Ser	synonymous_variant	Exon 5 of 11	ENST00000182527.4	NP_036420.1
TRAM2	XM_011515005.3	c.327C>T	p.Ser109Ser	synonymous_variant	Exon 4 of 10		XP_011513307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAM2	ENST00000182527.4	c.438C>T	p.Ser146Ser	synonymous_variant	Exon 5 of 11	1	NM_012288.4	ENSP00000182527.3
EFHC1	ENST00000637353.1	c.1852-13324G>A		intron_variant	Intron 10 of 10	5		ENSP00000490441.1
EFHC1	ENST00000636343.1	c.1516-6335G>A		intron_variant	Intron 8 of 8	5		ENSP00000490193.1
EFHC1	ENST00000637602.1	n.*1553-13324G>A		intron_variant	Intron 10 of 10	2		ENSP00000490074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461822 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: chr6-52374358;