rs138728

Variant names:

• chr22-35300084-G-C
• rs138728
• NM_005488.3:c.52+104G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-35300084-G-C
• chr22-35300084-G-A
• chr22-35300084-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005488.3(TOM1):​c.52+104G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,334,146 control chromosomes in the GnomAD database, including 259,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (22871 hom., cov: 35)
  • Exomes 𝑓: 0.63 (237103 hom.)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14
• Publications: 10 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 22-35300084-G-C is Benign according to our data. Variant chr22-35300084-G-C is described in ClinVar as Benign. ClinVar VariationId is 2687946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

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.52+104G>C		intron	N/A	NP_005479.1	O60784-1
	TOM1	NM_001135732.2		c.52+104G>C		intron	N/A	NP_001129204.1	O60784-2
	TOM1	NM_001135729.2		c.-48+706G>C		intron	N/A	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.52+104G>C		intron	N/A	ENSP00000394466.2	O60784-1
	TOM1	ENST00000411850.5	TSL:1	c.52+104G>C		intron	N/A	ENSP00000413697.1	O60784-2
	TOM1	ENST00000953252.1		c.52+104G>C		intron	N/A	ENSP00000623311.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 78080 AN: 152136 Hom.: 22887 Cov.: 35

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.628 AC: 742556 AN: 1181892 Hom.: 237103 AF XY: 0.628 AC XY: 371085 AN XY: 590930

African (AFR) AF: 0.188 AC: 5037 AN: 26786

American (AMR) AF: 0.566 AC: 18296 AN: 32352

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 15586 AN: 22698

East Asian (EAS) AF: 0.521 AC: 17943 AN: 34416

South Asian (SAS) AF: 0.579 AC: 42761 AN: 73874

European-Finnish (FIN) AF: 0.609 AC: 23367 AN: 38348

Middle Eastern (MID) AF: 0.594 AC: 2583 AN: 4350

European-Non Finnish (NFE) AF: 0.652 AC: 585811 AN: 898374

Other (OTH) AF: 0.615 AC: 31172 AN: 50694

GnomAD4 genome AF: 0.513 AC: 78061 AN: 152254 Hom.: 22871 Cov.: 35 AF XY: 0.513 AC XY: 38157 AN XY: 74448

African (AFR) AF: 0.209 AC: 8672 AN: 41538

American (AMR) AF: 0.561 AC: 8590 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2765 AN: 5176

South Asian (SAS) AF: 0.578 AC: 2792 AN: 4828

European-Finnish (FIN) AF: 0.618 AC: 6551 AN: 10608

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.651 AC: 44293 AN: 68008

Other (OTH) AF: 0.579 AC: 1223 AN: 2112

Alfa AF: 0.448 Hom.: 973

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		-1.1
PromoterAI		-0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs138728; hg19: chr22-35696077; COSMIC: COSV53334059; COSMIC: COSV53334059;