NM_138383.3:c.1790C>G

Variant names:

• chr16-70664131-G-C
• rs531163149
• NM_138383.3:c.1790C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_138383.3(MTSS2):​c.1790C>G​(p.Thr597Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,282 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T597M) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MTSS2 NM_138383.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89

Genes affected

MTSS2 (HGNC:25094): (MTSS I-BAR domain containing 2) Enables GTPase activator activity and small GTPase binding activity. Involved in activation of GTPase activity and cellular response to platelet-derived growth factor stimulus. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000279569 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-70664131-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTSS2	NM_138383.3	c.1790C>G	p.Thr597Arg	missense_variant	Exon 15 of 15	ENST00000338779.11	NP_612392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTSS2	ENST00000338779.11	c.1790C>G	p.Thr597Arg	missense_variant	Exon 15 of 15	1	NM_138383.3	ENSP00000341171.6
ENSG00000279569	ENST00000623414.1	n.2465G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000412 AC: 1 AN: 242448 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 132628

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458282 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 725620

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.3	D;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;.
Sift4G	Benign	0.081	T;T
Polyphen		1.0	D;.
Vest4		0.76
MutPred		0.25		Loss of phosphorylation at T597 (P = 0.0105);.;
MVP		0.29
MPC		0.28
ClinPred		0.97	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.80

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: rs531163149; hg19: chr16-70698034;