7-98856143-A-G

Position:

• chr7-98856143-A-G

Variant summary

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

The ENST00000339375.9(TMEM130):​c.592T>C​(p.Tyr198His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM130 ENST00000339375.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

Genes affected

TMEM130 (HGNC:25429): (transmembrane protein 130) Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM130 (HGNC:):

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, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM130	NM_152913.3	c.592T>C	p.Tyr198His	missense_variant	4/8	ENST00000339375.9	NP_690877.1
TMEM130	NM_001134450.2	c.592T>C	p.Tyr198His	missense_variant	4/8		NP_001127922.1
TMEM130	NM_001134451.2	c.286T>C	p.Tyr96His	missense_variant	3/7		NP_001127923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM130	ENST00000339375.9	c.592T>C	p.Tyr198His	missense_variant	4/8	1	NM_152913.3	ENSP00000341256.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461712 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727154

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2021

The c.592T>C (p.Y198H) alteration is located in exon 4 (coding exon 4) of the TMEM130 gene. This alteration results from a T to C substitution at nucleotide position 592, causing the tyrosine (Y) at amino acid position 198 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.86	D;D;D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.1	M;M;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.7	D;D;D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		0.99	D;D;.;D
Vest4		0.77
MutPred		0.87		Loss of stability (P = 0.1201);Loss of stability (P = 0.1201);.;.;
MVP		0.61
MPC		0.36
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.29
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-98453766;