7-75988260-G-T

Position:

• chr7-75988260-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031925.3(TMEM120A):​c.555C>A​(p.Asn185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 30)
• Consequence: TMEM120A NM_031925.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.244

Genes affected

TMEM120A (HGNC:21697): (transmembrane protein 120A) Predicted to enable ion channel activity. Involved in fat cell differentiation; protein heterooligomerization; and protein homooligomerization. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM120A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3679695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM120A	NM_031925.3	c.555C>A	p.Asn185Lys	missense_variant	6/12	ENST00000493111.7	NP_114131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM120A	ENST00000493111.7	c.555C>A	p.Asn185Lys	missense_variant	6/12	1	NM_031925.3	ENSP00000473983.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 30

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

Sep 02, 2024

The c.555C>A (p.N185K) alteration is located in exon 6 (coding exon 6) of the TMEM120A gene. This alteration results from a C to A substitution at nucleotide position 555, causing the asparagine (N) at amino acid position 185 to be replaced by a lysine (K). 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	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	17
DANN	Benign	0.78
DEOGEN2	Benign	0.37	T;D;.;.;.
FATHMM_MKL	Benign	0.55	D
LIST_S2	Pathogenic	0.99	D;.;D;D;D
MetaRNN	Benign	0.37	T;T;T;T;T
MutationAssessor	Pathogenic	3.4	M;.;.;.;.
PrimateAI	Uncertain	0.76	T
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		1.0	D;.;.;.;.
Vest4		0.99
MVP		0.10
GERP RS		-5.2
Varity_R		0.15
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr7-75617578;