X-153974136-G-C

Variant names:

• chrX-153974136-G-C
• rs2266887
• NM_003492.3:c.-214+1276G>C

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+1 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 1 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Supporting

The NM_003492.3(TMEM187):c.-214+1276G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000271 (AC=3) in the gnomAD database across 110,836 control chromosomes (no homozygotes or hemizygotes observed). The grpmax filtering allele frequency (95% CI) is 0.00000626. 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 0.000027 (0 hom., 0 hem., cov: 24)
• Consequence: TMEM187 NM_003492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 7 publications found

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]

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Very rare in gnomAD (popmax AF <0.01%) — O3 supporting; GnomAD effective popmax AF = 0.000006 — very rare (O3 supporting [+1])

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>C	intron	Intron 1 of 1	Prot: NP_003483.1 UniProt:

TMEM187 NM_003492.3

MANE Select

HGVSc / HGVSpc.-214+1276G>C

Exon rankIntron 1 of 1

intron

Prot: NP_003483.1UniProt: Q14656

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TMEM187 ENST00000369982.5	TSL:1MANE Select	c.-214+1276G>C	intron	Intron 1 of 1	Prot: ENSP00000358999.4 UniProt:
	TMEM187 ENST00000855602.1		c.-207+1276G>C	intron	Intron 1 of 1	Prot: ENSP00000525661.1 UniProt:
	TMEM187 ENST00000855603.1		c.-214+712G>C	intron	Intron 2 of 2	Prot: ENSP00000525662.1 UniProt:

TMEM187 ENST00000369982.5

TSL:1MANE Select

HGVSc / HGVSpc.-214+1276G>C

Exon rankIntron 1 of 1

intron

Prot: ENSP00000358999.4UniProt: Q14656

TMEM187 ENST00000855602.1

HGVSc / HGVSpc.-207+1276G>C

Exon rankIntron 1 of 1

intron

Prot: ENSP00000525661.1UniProt: Q14656

TMEM187 ENST00000855603.1

HGVSc / HGVSpc.-214+712G>C

Exon rankIntron 2 of 2

intron

Prot: ENSP00000525662.1UniProt: 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: 0.0000271	AC:3	Hom:0	AN:110836	Cov:24
GnomAD4 genome	AF: 0.0000271	AC:3	Hom:0	AN:110836	Cov:24
TOPMed (Bravo) Warning	AF: 0.000132	AC:35	Hom:10	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:2250	AN:28338	Cov:

Showing 4 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.19
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.15
GPN-Star LLR	N/A	2.8
GPN-Star score	N/A	-1.7
PhyloP100	Benign	-2.4

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.070
SpliceAI score (max)	Benign	0.010	Details are displayed if max score is > 0.2

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs2266887;

hg19: chrX-153239587;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar