rs2292181

Variant names:

• chr3-44861942-G-A
• rs2292181
• NM_144638.3:c.18G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-44861942-G-A
• chr3-44861942-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_144638.3(TMEM42):​c.18G>A​(p.Gly6Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000788 in 1,268,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: TMEM42 NM_144638.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 0 publications found

Genes affected

TMEM42 (HGNC:28444): (transmembrane protein 42) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MIR564 (HGNC:32820): (microRNA 564) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

KIF15 (HGNC:17273): (kinesin family member 15) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIF15 Gene-Disease associations (from GenCC):

• braddock-carey syndrome 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000304717 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144638.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM42	NM_144638.3	MANE Select	c.18G>A	p.Gly6Gly	synonymous	Exon 1 of 3	NP_653239.1
	MIR564	NR_030290.1		n.55G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM42	ENST00000302392.5	TSL:1 MANE Select	c.18G>A	p.Gly6Gly	synonymous	Exon 1 of 3	ENSP00000306564.4
	TMEM42	ENST00000477126.1	TSL:1	n.39G>A		non_coding_transcript_exon	Exon 1 of 2
	TMEM42	ENST00000891869.1		c.18G>A	p.Gly6Gly	synonymous	Exon 1 of 3	ENSP00000561928.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.88e-7 AC: 1 AN: 1268298 Hom.: 0 Cov.: 31 AF XY: 0.00000162 AC XY: 1 AN XY: 618962

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24840

American (AMR) AF: 0.00 AC: 0 AN: 16938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19334

East Asian (EAS) AF: 0.00 AC: 0 AN: 28044

South Asian (SAS) AF: 0.00 AC: 0 AN: 63578

European-Finnish (FIN) AF: 0.0000274 AC: 1 AN: 36460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4894

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1022274

Other (OTH) AF: 0.00 AC: 0 AN: 51936

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.2
DANN	Benign	0.84
PhyloP100		1.1
PromoterAI		-0.080	Neutral

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

Other links and lift over

dbSNP: rs2292181; hg19: chr3-44903434;