chr3-44861942-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_144638.3(TMEM42):​c.18G>C​(p.Gly6Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 1,420,196 control chromosomes in the GnomAD database, including 1,794 homozygotes. 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: 𝑓 0.054 (234 hom., cov: 33)
  • Exomes 𝑓: 0.048 (1560 hom.)
• Consequence: TMEM42 NM_144638.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 15 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

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>C	p.Gly6Gly	synonymous	Exon 1 of 3	NP_653239.1
	MIR564	NR_030290.1		n.55G>C		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>C	p.Gly6Gly	synonymous	Exon 1 of 3	ENSP00000306564.4
	TMEM42	ENST00000477126.1	TSL:1	n.39G>C		non_coding_transcript_exon	Exon 1 of 2
	TMEM42	ENST00000891869.1		c.18G>C	p.Gly6Gly	synonymous	Exon 1 of 3	ENSP00000561928.1

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8196 AN: 152172 Hom.: 234 Cov.: 33

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0748

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.0688

GnomAD2 exomes AF: 0.0528 AC: 1798 AN: 34078 AF XY: 0.0510

Gnomad AFR exome AF: 0.0534

Gnomad AMR exome AF: 0.0696

Gnomad ASJ exome AF: 0.0688

Gnomad EAS exome AF: 0.0440

Gnomad FIN exome AF: 0.0400

Gnomad NFE exome AF: 0.0510

Gnomad OTH exome AF: 0.0586

GnomAD4 exome AF: 0.0484 AC: 61392 AN: 1267912 Hom.: 1560 Cov.: 31 AF XY: 0.0487 AC XY: 30112 AN XY: 618742

African (AFR) AF: 0.0519 AC: 1289 AN: 24834

American (AMR) AF: 0.0741 AC: 1253 AN: 16908

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 1091 AN: 19318

East Asian (EAS) AF: 0.0469 AC: 1315 AN: 28042

South Asian (SAS) AF: 0.0441 AC: 2803 AN: 63534

European-Finnish (FIN) AF: 0.0388 AC: 1414 AN: 36436

Middle Eastern (MID) AF: 0.0799 AC: 391 AN: 4892

European-Non Finnish (NFE) AF: 0.0481 AC: 49204 AN: 1022032

Other (OTH) AF: 0.0507 AC: 2632 AN: 51916

GnomAD4 genome AF: 0.0539 AC: 8208 AN: 152284 Hom.: 234 Cov.: 33 AF XY: 0.0533 AC XY: 3969 AN XY: 74470

African (AFR) AF: 0.0527 AC: 2193 AN: 41580

American (AMR) AF: 0.0747 AC: 1144 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3472

East Asian (EAS) AF: 0.0545 AC: 281 AN: 5152

South Asian (SAS) AF: 0.0437 AC: 211 AN: 4832

European-Finnish (FIN) AF: 0.0345 AC: 366 AN: 10620

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0536 AC: 3643 AN: 68002

Other (OTH) AF: 0.0681 AC: 144 AN: 2116

Alfa AF: 0.0575 Hom.: 31

Bravo AF: 0.0556

Asia WGS AF: 0.0470 AC: 165 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.8
DANN	Benign	0.55
PhyloP100		1.1
PromoterAI		-0.18	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV56643703;