Genetic Variant TMEM187:c.-214+1276G>T (chrX-153974136-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_003492.3(TMEM187):c.-214+1276G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.382 (AC=42,391) in the gnomAD database across 110,857 control chromosomes, including 7,987 homozygotes and 12,685 hemizygotes. The grpmax filtering allele frequency (95% CI) is 0.731. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 7987 hom., 12685 hem., cov: 24)

Consequence

TMEM187
NM_003492.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.36

Publications

7 publications found

Variant links:

Genes affected

TMEM187 (HGNC:13705): (transmembrane protein 187) This gene consists of two exons and encodes a multi-pass membrane protein. An alternatively spliced transcript variant encoding the same protein has been found, but its biological validity is not determined. [provided by RefSeq, May 2010]

TMEM187 links:

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new If you want to explore the variant's impact on the transcript NM_003492.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.7307 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_003492.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM187	NM_003492.3	MANE Select	c.-214+1276G>T		intron	N/A	NP_003483.1	Q14656

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM187	ENST00000369982.5	TSL:1 MANE Select	c.-214+1276G>T	intron	N/A	ENSP00000358999.4	Q14656
TMEM187	ENST00000855602.1		c.-207+1276G>T	intron	N/A	ENSP00000525661.1	Q14656
TMEM187	ENST00000855603.1		c.-214+712G>T	intron	N/A	ENSP00000525662.1	Q14656

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.382	AC:42328	Hom:7978	AN:110802	Cov:24
GnomAD4 genome	AF: 0.382	AC:42391	Hom:7987	AN:110857	Cov:24
TOPMed (Bravo)	AF: 0.424	AC:112191	Hom:42310	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.225	AC:6386	Hom:2250	AN:28338	Cov:
Local & regional cohorts 7 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.402	AC:769	Hom:139	AN:1915	Cov:
Denmark Genome	AF: 0.120	AC:28	Hom:	AN:233	Cov:
Korea4K (4,157 Koreans)	AF: 0.737	AC:3849	Hom:	AN:5222	Cov:
Qatari Genome	AF: 0.557	AC:49	Hom:	AN:88	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.755	AC:77010	Hom:23126	AN:102058	Cov:
Turkish Variome	AF: 0.382	AC:557	Hom:211	AN:1460	Cov:
UK10K	AF: 0.176	AC:1161	Hom:	AN:6597	Cov:

Showing 11 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Benign	-	0.11
BayesDel_noAF	Benign	-	-0.92
CADD	Benign	-	0.49
DANN	Benign	-	0.39
GPN-Star LLR	N/A	-	4.0
GPN-Star score	N/A	-	-0.25
Mutation Taster	N/A	polymorphism (auto)	100/0
PhyloP100	Benign	-	-2.4

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.0
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over