chr6-10763546-TA-T

Variant names:

• chr6-10763546-TA-T
• rs35696238
• NM_001242957.3:c.*905delT

Variant summary

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

The NM_001242957.3(MAK):​c.*905delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (46547 hom., cov: 0)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: MAK NM_001242957.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.973
• 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 -10 ACMG points.

• BP6: Variant 6-10763546-TA-T is Benign according to our data. Variant chr6-10763546-TA-T is described in ClinVar as Benign. ClinVar VariationId is 354775.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 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.*905delT		3_prime_UTR	Exon 15 of 15	NP_001229886.1	P20794-2
	MAK	NM_005906.6		c.*905delT		3_prime_UTR	Exon 14 of 14	NP_005897.1	A0A140VK28
	MAK	NM_001242385.2		c.*905delT		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.*905delT		3_prime_UTR	Exon 15 of 15	ENSP00000346484.3	P20794-2
	MAK	ENST00000474039.5	TSL:1	c.*905delT		3_prime_UTR	Exon 14 of 14	ENSP00000476067.1	P20794-1
	MAK	ENST00000536370.6	TSL:1	c.*905delT		3_prime_UTR	Exon 13 of 13	ENSP00000442221.2	P20794-3

Frequencies

GnomAD3 genomes AF: 0.819 AC: 114180 AN: 139430 Hom.: 46544 Cov.: 0

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.787

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

⚠️ 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) 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

⚠️ 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 AF: 0.819 AC: 114205 AN: 139466 Hom.: 46547 Cov.: 0 AF XY: 0.819 AC XY: 55056 AN XY: 67186

African (AFR) AF: 0.911 AC: 34305 AN: 37644

American (AMR) AF: 0.774 AC: 10827 AN: 13992

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2325 AN: 3288

East Asian (EAS) AF: 0.915 AC: 4434 AN: 4844

South Asian (SAS) AF: 0.802 AC: 3455 AN: 4308

European-Finnish (FIN) AF: 0.832 AC: 6544 AN: 7868

Middle Eastern (MID) AF: 0.772 AC: 207 AN: 268

European-Non Finnish (NFE) AF: 0.775 AC: 49935 AN: 64470

Other (OTH) AF: 0.786 AC: 1499 AN: 1906

Alfa AF: 0.674 Hom.: 1288

ClinVar

ClinVar submissions as Germline

Significance: 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		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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;