Genetic Variant NM_003492.3:c.-214+1276G>A (chrX-153974136-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_003492.3(TMEM187):c.-214+1276G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. 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: not found (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: Likely_benign. The variant received -2 points.

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	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).

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>A	intron	Intron 1 of 1	Prot: NP_003483.1 UniProt: Q14656

TMEM187 NM_003492.3

MANE Select

HGVSc / HGVSpc.-214+1276G>A

Exon rankIntron 1 of 1

intron

Prot: NP_003483.1UniProt: Q14656

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
TMEM187 ENST00000369982.5	TSL:1MANE Select	c.-214+1276G>A	intron	Intron 1 of 1	Prot: ENSP00000358999.4 UniProt: Q14656
TMEM187 ENST00000855602.1		c.-207+1276G>A	intron	Intron 1 of 1	Prot: ENSP00000525661.1 UniProt: Q14656
TMEM187 ENST00000855603.1		c.-214+712G>A	intron	Intron 2 of 2	Prot: ENSP00000525662.1 UniProt: Q14656

TMEM187 ENST00000369982.5

TSL:1MANE Select

HGVSc / HGVSpc.-214+1276G>A

Exon rankIntron 1 of 1

intron

Prot: ENSP00000358999.4UniProt: Q14656

TMEM187 ENST00000855602.1

HGVSc / HGVSpc.-207+1276G>A

Exon rankIntron 1 of 1

intron

Prot: ENSP00000525661.1UniProt: Q14656

TMEM187 ENST00000855603.1

HGVSc / HGVSpc.-214+712G>A

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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:24
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:24
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:2250	AN:28338	Cov:

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score
AlphaGenome AVI	Benign	0.13
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.94
GPN-Star LLR	N/A	1.9
GPN-Star score	N/A	-1.9
PhyloP100	Benign	-2.4

Showing 7 of 7 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.

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

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence