7-40132906-T-C

Variant names:

• chr7-40132906-T-C
• rs12146
• NM_138701.4:c.*153A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138701.4(MPLKIP):​c.*153A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 562,914 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: 0.0000018 (0 hom.)
• Consequence: MPLKIP NM_138701.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 0 publications found

Genes affected

MPLKIP (HGNC:16002): (M-phase specific PLK1 interacting protein) The protein encoded by this gene localizes to the centrosome during mitosis and to the midbody during cytokinesis. The protein is phosphorylated by cyclin-dependent kinase 1 during mitosis and subsequently interacts with polo-like kinase 1. The protein is thought to function in regulating mitosis and cytokinesis. Mutations in this gene result in nonphotosensitive trichothiodystrophy. [provided by RefSeq, Nov 2009]

MPLKIP Gene-Disease associations (from GenCC):

• trichothiodystrophy 4, nonphotosensitive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• trichothiodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138701.4. 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
	MPLKIP	NM_138701.4	MANE Select	c.*153A>G		3_prime_UTR	Exon 2 of 2	NP_619646.1	Q8TAP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPLKIP	ENST00000306984.8	TSL:1 MANE Select	c.*153A>G		3_prime_UTR	Exon 2 of 2	ENSP00000304553.5	Q8TAP9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000178 AC: 1 AN: 562914 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 299476

⚠️ 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: 14684

American (AMR) AF: 0.00 AC: 0 AN: 26460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17760

East Asian (EAS) AF: 0.00 AC: 0 AN: 31688

South Asian (SAS) AF: 0.00 AC: 0 AN: 54436

European-Finnish (FIN) AF: 0.0000295 AC: 1 AN: 33948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 351328

Other (OTH) AF: 0.00 AC: 0 AN: 30326

⚠️ 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	-0.88
CADD	Benign	2.8
DANN	Benign	0.53
PhyloP100		0.14

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: rs12146; hg19: chr7-40172505;