6-10763546-TAAAAA-TAAA

Variant names:

• chr6-10763546-TAA-T
• rs35696238
• NM_001242957.3:c.*904_*905delTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001242957.3(MAK):​c.*904_*905delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 139,374 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 0)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: MAK NM_001242957.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.941
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242957.3. 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
	MAK	NM_001242957.3	MANE Select	c.*904_*905delTT		3_prime_UTR	Exon 15 of 15	NP_001229886.1	P20794-2
	MAK	NM_005906.6		c.*904_*905delTT		3_prime_UTR	Exon 14 of 14	NP_005897.1	A0A140VK28
	MAK	NM_001242385.2		c.*904_*905delTT		3_prime_UTR	Exon 13 of 13	NP_001229314.1	P20794-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAK	ENST00000354489.7	TSL:5 MANE Select	c.*904_*905delTT		3_prime_UTR	Exon 15 of 15	ENSP00000346484.3	P20794-2
	MAK	ENST00000474039.5	TSL:1	c.*904_*905delTT		3_prime_UTR	Exon 14 of 14	ENSP00000476067.1	P20794-1
	MAK	ENST00000536370.6	TSL:1	c.*904_*905delTT		3_prime_UTR	Exon 13 of 13	ENSP00000442221.2	P20794-3

Frequencies

GnomAD3 genomes AF: 0.00293 AC: 408 AN: 139336 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00315

Gnomad ASJ AF: 0.00122

Gnomad EAS AF: 0.00206

Gnomad SAS AF: 0.000923

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.00475

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00296 AC: 413 AN: 139372 Hom.: 0 Cov.: 0 AF XY: 0.00322 AC XY: 216 AN XY: 67118

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

African (AFR) AF: 0.00183 AC: 69 AN: 37634

American (AMR) AF: 0.00329 AC: 46 AN: 13988

Ashkenazi Jewish (ASJ) AF: 0.00122 AC: 4 AN: 3292

East Asian (EAS) AF: 0.00227 AC: 11 AN: 4844

South Asian (SAS) AF: 0.000929 AC: 4 AN: 4308

European-Finnish (FIN) AF: 0.0155 AC: 121 AN: 7808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.00231 AC: 149 AN: 64448

Other (OTH) AF: 0.00473 AC: 9 AN: 1904

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism

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: rs35696238; hg19: chr6-10763779;