rs57755951

Variant names:

• chr22-35317938-C-T
• rs57755951
• NM_005488.3:c.114C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_005488.3(TOM1):​c.114C>T​(p.Asp38Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.00261 in 1,614,132 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (47 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (54 hom.)
• Consequence: TOM1 NM_005488.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.17
• Publications: 1 publications found

Genes affected

TOM1 (HGNC:11982): (target of myb1 membrane trafficking protein) This gene was identified as a target of the v-myb oncogene. The encoded protein shares its N-terminal domain in common with proteins associated with vesicular trafficking at the endosome. It is recruited to the endosomes by its interaction with endofin. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

TOM1 Gene-Disease associations (from GenCC):

• immune system disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• immunodeficiency 85 and autoimmunity

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.124).
• BP6: Variant 22-35317938-C-T is Benign according to our data. Variant chr22-35317938-C-T is described in ClinVar as Benign. ClinVar VariationId is 778918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0142 (2159/152278) while in subpopulation AFR AF = 0.0494 (2054/41550). AF 95% confidence interval is 0.0477. There are 47 homozygotes in GnomAd4. There are 1004 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2159 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005488.3. 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
	TOM1	NM_005488.3	MANE Select	c.114C>T	p.Asp38Asp	synonymous	Exon 2 of 15	NP_005479.1	O60784-1
	TOM1	NM_001135732.2		c.114C>T	p.Asp38Asp	synonymous	Exon 2 of 15	NP_001129204.1	O60784-2
	TOM1	NM_001135729.2		c.15C>T	p.Asp5Asp	synonymous	Exon 2 of 15	NP_001129201.1	O60784-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOM1	ENST00000449058.7	TSL:1 MANE Select	c.114C>T	p.Asp38Asp	synonymous	Exon 2 of 15	ENSP00000394466.2	O60784-1
	TOM1	ENST00000411850.5	TSL:1	c.114C>T	p.Asp38Asp	synonymous	Exon 2 of 15	ENSP00000413697.1	O60784-2
	TOM1	ENST00000929704.1		c.112C>T	p.His38Tyr	missense	Exon 2 of 14	ENSP00000599763.1

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2153 AN: 152160 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00366 AC: 920 AN: 251482 AF XY: 0.00259

Gnomad AFR exome AF: 0.0498

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00141 AC: 2058 AN: 1461854 Hom.: 54 Cov.: 31 AF XY: 0.00126 AC XY: 913 AN XY: 727234

African (AFR) AF: 0.0485 AC: 1622 AN: 33474

American (AMR) AF: 0.00239 AC: 107 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0000953 AC: 106 AN: 1111980

Other (OTH) AF: 0.00341 AC: 206 AN: 60396

GnomAD4 genome AF: 0.0142 AC: 2159 AN: 152278 Hom.: 47 Cov.: 32 AF XY: 0.0135 AC XY: 1004 AN XY: 74472

African (AFR) AF: 0.0494 AC: 2054 AN: 41550

American (AMR) AF: 0.00490 AC: 75 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68018

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.0122 Hom.: 38

Bravo AF: 0.0159

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=238/62	polymorphism

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: rs57755951; hg19: chr22-35713931;