rs527512238

Variant names:

• chr1-155209154-T-A
• rs527512238
• NM_002455.5:c.350T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-155209154-T-A
• chr1-155209154-T-C
• chr1-155209154-T-G

Variant summary

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

The NM_001407556.1(THBS3):​c.-284A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000088 in 1,363,496 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: 0.0000088 (0 hom.)
• Consequence: THBS3 NM_001407556.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.16

Genes affected

MTX1 (HGNC:7504): (metaxin 1) Predicted to be involved in mitochondrion organization. Part of MIB complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

THBS3 (HGNC:11787): (thrombospondin 3) The protein encoded by this gene belongs to the thrombospondin family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentameric molecule linked by a single disulfide bond. This gene shares a common promoter with metaxin 1. Alternate splicing results in coding and non-coding transcript variants. [provided by RefSeq, Nov 2011]

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=0.04104662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTX1	NM_002455.5	c.350T>A	p.Leu117Gln	missense_variant	Exon 1 of 8	ENST00000368376.8	NP_002446.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTX1	ENST00000368376.8	c.350T>A	p.Leu117Gln	missense_variant	Exon 1 of 8	1	NM_002455.5	ENSP00000357360.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000168 AC: 2 AN: 119070 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65420

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000477

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000880 AC: 12 AN: 1363496 Hom.: 0 Cov.: 34 AF XY: 0.00000747 AC XY: 5 AN XY: 669230

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: 0.0000113

Gnomad4 OTH exome AF: 0.00

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	0.053
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.016
DANN	Benign	0.49
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.0090
Sift	Benign	0.34	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.0	B;B
Vest4		0.042
MutPred		0.31		Gain of MoRF binding (P = 0.0752);Gain of MoRF binding (P = 0.0752);
MVP		0.048
MPC		0.25
ClinPred		0.32	T
GERP RS		-8.4
Varity_R		0.048
gMVP		0.12

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: rs527512238; hg19: chr1-155178945;