rs760077

Variant names:

• chr1-155208991-T-A
• rs760077
• NM_002455.5:c.187T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-155208991-T-A
• chr1-155208991-T-C
• chr1-155208991-T-G

Variant summary

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

The NM_002455.5(MTX1):​c.187T>A​(p.Ser63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,599,114 control chromosomes in the GnomAD database, including 121,197 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10163 hom., cov: 32)
  • Exomes 𝑓: 0.39 (111034 hom.)
• Consequence: MTX1 NM_002455.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610
• Publications: 80 publications found

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]

THBS3 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002467364).
• BP6: Variant 1-155208991-T-A is Benign according to our data. Variant chr1-155208991-T-A is described in ClinVar as Benign. ClinVar VariationId is 767706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002455.5. 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
	MTX1	NM_002455.5	MANE Select	c.187T>A	p.Ser63Thr	missense	Exon 1 of 8	NP_002446.3
	MTX1	NM_198883.3		c.187T>A	p.Ser63Thr	missense	Exon 1 of 7	NP_942584.2	Q13505-2
	THBS3	NM_001407556.1		c.-121A>T		5_prime_UTR	Exon 1 of 23	NP_001394485.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTX1	ENST00000368376.8	TSL:1 MANE Select	c.187T>A	p.Ser63Thr	missense	Exon 1 of 8	ENSP00000357360.3	Q13505-1
	MTX1	ENST00000316721.8	TSL:1	c.187T>A	p.Ser63Thr	missense	Exon 1 of 7	ENSP00000317106.4	Q13505-2
	THBS3	ENST00000486260.5	TSL:5	n.61A>T		non_coding_transcript_exon	Exon 1 of 14

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55030 AN: 151842 Hom.: 10154 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.387 AC: 559728 AN: 1447152 Hom.: 111034 Cov.: 73 AF XY: 0.390 AC XY: 280180 AN XY: 718794

African (AFR) AF: 0.326 AC: 10854 AN: 33306

American (AMR) AF: 0.205 AC: 8825 AN: 43066

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11712 AN: 25816

East Asian (EAS) AF: 0.172 AC: 6732 AN: 39190

South Asian (SAS) AF: 0.396 AC: 33544 AN: 84670

European-Finnish (FIN) AF: 0.375 AC: 18645 AN: 49660

Middle Eastern (MID) AF: 0.495 AC: 2729 AN: 5510

European-Non Finnish (NFE) AF: 0.401 AC: 443257 AN: 1106254

Other (OTH) AF: 0.393 AC: 23430 AN: 59680

GnomAD4 genome AF: 0.362 AC: 55058 AN: 151962 Hom.: 10163 Cov.: 32 AF XY: 0.361 AC XY: 26839 AN XY: 74274

African (AFR) AF: 0.323 AC: 13374 AN: 41462

American (AMR) AF: 0.290 AC: 4435 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1057 AN: 5126

South Asian (SAS) AF: 0.407 AC: 1962 AN: 4824

European-Finnish (FIN) AF: 0.377 AC: 3991 AN: 10574

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.402 AC: 27329 AN: 67904

Other (OTH) AF: 0.365 AC: 771 AN: 2112

Alfa AF: 0.404 Hom.: 4054

Bravo AF: 0.347

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0025	T
PhyloP100		-0.061
Sift4G	Pathogenic	0.0	D
Vest4		0.10
PromoterAI		0.026	Neutral
gMVP		0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs760077; hg19: chr1-155178782;