chr7-1547758-C-G

Position:

• chr7-1547758-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001097620.2(TMEM184A):​c.996G>C​(p.Lys332Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM184A NM_001097620.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63

Genes affected

TMEM184A (HGNC:28797): (transmembrane protein 184A) Predicted to enable heparin binding activity. Predicted to act upstream of or within germ-line sex determination; regulation of protein localization; and regulation of secretion. Predicted to be located in cytoplasmic vesicle; perinuclear region of cytoplasm; and plasma membrane. Predicted to be active in early endosome membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM184A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM184A	NM_001097620.2	c.996G>C	p.Lys332Asn	missense_variant	8/9	ENST00000297477.10	NP_001091089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM184A	ENST00000297477.10	c.996G>C	p.Lys332Asn	missense_variant	8/9	1	NM_001097620.2	ENSP00000297477.4
TMEM184A	ENST00000319018.12	n.*419G>C		non_coding_transcript_exon_variant	7/8	5		ENSP00000326348.7
TMEM184A	ENST00000468535.5	n.1874G>C		non_coding_transcript_exon_variant	5/6	2
TMEM184A	ENST00000319018.12	n.*419G>C		3_prime_UTR_variant	7/8	5		ENSP00000326348.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Feb 28, 2024

The c.996G>C (p.K332N) alteration is located in exon 8 (coding exon 7) of the TMEM184A gene. This alteration results from a G to C substitution at nucleotide position 996, causing the lysine (K) at amino acid position 332 to be replaced by an asparagine (N). 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	Benign	0.30
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.14
Sift	Benign	0.31	T
Sift4G	Benign	0.28	T
Polyphen		0.048	B
Vest4		0.68
MutPred		0.50		Loss of methylation at K332 (P = 0.0013);
MVP		0.25
MPC		0.082
ClinPred		0.56	D
GERP RS		3.7
Varity_R		0.18
gMVP		0.78

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: chr7-1587394;