6-10763850-CAAA-CAAAA

Variant names:

• chr6-10763850-C-CA
• rs60516370
• NM_001242957.3:c.*601dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001242957.3(MAK):​c.*601dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (33299 hom., cov: 0)
  • Exomes 𝑓: 0.18 (0 hom.)
• Consequence: MAK NM_001242957.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.957
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 6-10763850-C-CA is Benign according to our data. Variant chr6-10763850-C-CA is described in ClinVar as Likely_benign. ClinVar VariationId is 354777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 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.*601dupT		3_prime_UTR	Exon 15 of 15	NP_001229886.1	P20794-2
	MAK	NM_005906.6		c.*601dupT		3_prime_UTR	Exon 14 of 14	NP_005897.1	A0A140VK28
	MAK	NM_001242385.2		c.*601dupT		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.*601dupT		3_prime_UTR	Exon 15 of 15	ENSP00000346484.3	P20794-2
	MAK	ENST00000474039.5	TSL:1	c.*601dupT		3_prime_UTR	Exon 14 of 14	ENSP00000476067.1	P20794-1
	MAK	ENST00000536370.6	TSL:1	c.*601dupT		3_prime_UTR	Exon 13 of 13	ENSP00000442221.2	P20794-3

Frequencies

GnomAD3 genomes AF: 0.693 AC: 95248 AN: 137476 Hom.: 33317 Cov.: 0

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.693

GnomAD4 exome AF: 0.182 AC: 8 AN: 44 Hom.: 0 Cov.: 0 AF XY: 0.179 AC XY: 5 AN XY: 28

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.125 AC: 1 AN: 8

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.100 AC: 1 AN: 10

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 6 AN: 24

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000313795), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.693 AC: 95221 AN: 137490 Hom.: 33299 Cov.: 0 AF XY: 0.697 AC XY: 46146 AN XY: 66242

African (AFR) AF: 0.482 AC: 17239 AN: 35772

American (AMR) AF: 0.707 AC: 9744 AN: 13776

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2310 AN: 3304

East Asian (EAS) AF: 0.906 AC: 4365 AN: 4818

South Asian (SAS) AF: 0.804 AC: 3576 AN: 4446

European-Finnish (FIN) AF: 0.824 AC: 6368 AN: 7732

Middle Eastern (MID) AF: 0.704 AC: 183 AN: 260

European-Non Finnish (NFE) AF: 0.766 AC: 49506 AN: 64648

Other (OTH) AF: 0.692 AC: 1285 AN: 1856

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Retinitis Pigmentosa, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs60516370; hg19: chr6-10764083;