chr7-40132833-C-A

Variant names:

• chr7-40132833-C-A
• rs11974850
• NM_138701.4:c.*226G>T

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.*226G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000503 in 397,792 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: 0.0000050 (0 hom.)
• Consequence: MPLKIP NM_138701.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• 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=-0.76).

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.*226G>T		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.*226G>T		3_prime_UTR	Exon 2 of 2	ENSP00000304553.5	Q8TAP9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000503 AC: 2 AN: 397792 Hom.: 0 Cov.: 3 AF XY: 0.00000472 AC XY: 1 AN XY: 211918

African (AFR) AF: 0.00 AC: 0 AN: 11446

American (AMR) AF: 0.00 AC: 0 AN: 16584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12092

East Asian (EAS) AF: 0.00 AC: 0 AN: 26234

South Asian (SAS) AF: 0.00 AC: 0 AN: 43392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1724

European-Non Finnish (NFE) AF: 0.00000833 AC: 2 AN: 240014

Other (OTH) AF: 0.00 AC: 0 AN: 23024

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		0.073

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: rs11974850; hg19: chr7-40172432;