NM_005488.3:c.379G>C

Variant names:

• chr22-35323508-G-C
• NM_005488.3:c.379G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005488.3(TOM1):​c.379G>C​(p.Ala127Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 6.8e-7 (0 hom.)
• Consequence: TOM1 NM_005488.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.73

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOM1	NM_005488.3	c.379G>C	p.Ala127Pro	missense_variant	Exon 5 of 15	ENST00000449058.7	NP_005479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOM1	ENST00000449058.7	c.379G>C	p.Ala127Pro	missense_variant	Exon 5 of 15	1	NM_005488.3	ENSP00000394466.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727232

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: 8.99e-7

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
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;T;T;.;T;.;T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	4.0	.;.;.;.;H;H;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.5	.;D;.;D;D;D;.;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0020	.;D;.;D;D;D;.;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D
Polyphen		1.0	.;.;.;.;D;D;.;.
Vest4		0.97, 0.97, 0.96, 0.93
MutPred		0.83		.;.;.;.;Gain of disorder (P = 0.0879);Gain of disorder (P = 0.0879);Gain of disorder (P = 0.0879);.;
MVP		0.77
MPC		1.1
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.93
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 11

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: chr22-35719501;