chrX-153974136-G-T

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

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
• 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 ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

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	Intron 1 of 1	Prot: NP_003483.1 UniProt:

TMEM187 NM_003492.3

MANE Select

HGVSc / HGVSpc.-214+1276G>T

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>T	intron	Intron 1 of 1	Prot: ENSP00000358999.4 UniProt:
	TMEM187 ENST00000855602.1		c.-207+1276G>T	intron	Intron 1 of 1	Prot: ENSP00000525661.1 UniProt:
	TMEM187 ENST00000855603.1		c.-214+712G>T	intron	Intron 2 of 2	Prot: ENSP00000525662.1 UniProt:

TMEM187 ENST00000369982.5

TSL:1MANE Select

HGVSc / HGVSpc.-214+1276G>T

Exon rankIntron 1 of 1

intron

Prot: ENSP00000358999.4UniProt: Q14656

TMEM187 ENST00000855602.1

HGVSc / HGVSpc.-207+1276G>T

Exon rankIntron 1 of 1

intron

Prot: ENSP00000525661.1UniProt: Q14656

TMEM187 ENST00000855603.1

HGVSc / HGVSpc.-214+712G>T

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: 0.382	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

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
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	100/0	polymorphism (auto)
PhyloP100	Benign	-2.4

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	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