NM_001242957.3:c.*600_*601dupTT

Variant names:

• chr6-10763850-C-CAA
• rs60516370
• NM_001242957.3:c.*600_*601dupTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001242957.3(MAK):​c.*600_*601dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0020 (2 hom., cov: 0)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: MAK NM_001242957.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957

Genes affected

MAK (HGNC:6816): (male germ cell associated kinase) The product of this gene is a serine/threonine protein kinase related to kinases involved in cell cycle regulation. Studies of the mouse and rat homologs have localized the kinase to the chromosomes during meiosis in spermatogenesis, specifically to the synaptonemal complex that exists while homologous chromosomes are paired. Mutations in this gene have been associated with ciliary defects resulting in retinitis pigmentosa 62. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TMEM14B (HGNC:21384): (transmembrane protein 14B) Enables identical protein binding activity. Involved in cerebral cortex development; neural precursor cell proliferation; and regulation of G1/S transition of mitotic cell cycle. Predicted to be integral component of membrane. Predicted to be active in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272162 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00201 (276/137500) while in subpopulation EAS AF= 0.00664 (32/4818). AF 95% confidence interval is 0.00483. There are 2 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAK	NM_001242957.3	c.*600_*601dupTT		3_prime_UTR_variant	Exon 15 of 15	ENST00000354489.7	NP_001229886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAK	ENST00000354489	c.*600_*601dupTT		3_prime_UTR_variant	Exon 15 of 15	5	NM_001242957.3	ENSP00000346484.3
ENSG00000272162	ENST00000480294.1	n.100+14166_100+14167dupAA		intron_variant	Intron 3 of 18	2		ENSP00000417929.1

Frequencies

GnomAD3 genomes AF: 0.00199 AC: 274 AN: 137490 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.000755

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.00116

Gnomad ASJ AF: 0.000605

Gnomad EAS AF: 0.00662

Gnomad SAS AF: 0.00134

Gnomad FIN AF: 0.00404

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00195

Gnomad OTH AF: 0.00269

GnomAD4 exome AF: 0.0455 AC: 2 AN: 44 Hom.: 0 Cov.: 0 AF XY: 0.0357 AC XY: 1 AN XY: 28

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0833

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00201 AC: 276 AN: 137500 Hom.: 2 Cov.: 0 AF XY: 0.00219 AC XY: 145 AN XY: 66218

Gnomad4 AFR AF: 0.000753

Gnomad4 AMR AF: 0.00116

Gnomad4 ASJ AF: 0.000605

Gnomad4 EAS AF: 0.00664

Gnomad4 SAS AF: 0.00135

Gnomad4 FIN AF: 0.00404

Gnomad4 NFE AF: 0.00196

Gnomad4 OTH AF: 0.00322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60516370; hg19: chr6-10764083;