chr22-35323167-A-C

Variant names:

• chr22-35323167-A-C
• rs761517973
• NM_005488.3:c.356A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005488.3(TOM1):​c.356A>C​(p.Asn119Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 32)
• Consequence: TOM1 NM_005488.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05093032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOM1	NM_005488.3	c.356A>C	p.Asn119Thr	missense_variant	Exon 4 of 15	ENST00000449058.7	NP_005479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOM1	ENST00000449058.7	c.356A>C	p.Asn119Thr	missense_variant	Exon 4 of 15	1	NM_005488.3	ENSP00000394466.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.0
DANN	Benign	0.95
DEOGEN2	Benign	0.019	T;.;T;T;.;.;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.74	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.051	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.38	.;.;.;.;N;N;N;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	.;N;.;N;N;N;N;.;N
REVEL	Benign	0.069
Sift	Benign	0.22	.;T;.;T;T;T;T;.;T
Sift4G	Benign	0.23	T;T;T;T;T;T;T;T;T
Polyphen		0.0	.;.;.;.;B;B;B;.;.
Vest4		0.11, 0.10, 0.14, 0.10, 0.097
MutPred		0.40		.;.;.;.;Gain of ubiquitination at K116 (P = 0.1117);Gain of ubiquitination at K116 (P = 0.1117);Gain of ubiquitination at K116 (P = 0.1117);Gain of ubiquitination at K116 (P = 0.1117);.;
MVP		0.18
MPC		0.29
ClinPred		0.14	T
GERP RS		-4.8
Varity_R		0.060
gMVP		0.091

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: rs761517973; hg19: chr22-35719160;