rs501948

Variant names:

• chr6-10762764-G-T
• rs501948
• NM_001242957.3:c.*1688C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-10762764-G-T
• chr6-10762764-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001242957.3(MAK):​c.*1688C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,624 control chromosomes in the GnomAD database, including 53,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (53012 hom., cov: 32)
  • Exomes 𝑓: 0.84 (151 hom.)
• Consequence: MAK NM_001242957.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-10762764-G-T is Benign according to our data. Variant chr6-10762764-G-T is described in ClinVar as Benign. ClinVar VariationId is 354768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 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.*1688C>A		3_prime_UTR	Exon 15 of 15	NP_001229886.1	P20794-2
	MAK	NM_005906.6		c.*1688C>A		3_prime_UTR	Exon 14 of 14	NP_005897.1	A0A140VK28
	MAK	NM_001242385.2		c.*1688C>A		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.*1688C>A		3_prime_UTR	Exon 15 of 15	ENSP00000346484.3	P20794-2
	MAK	ENST00000474039.5	TSL:1	c.*1688C>A		3_prime_UTR	Exon 14 of 14	ENSP00000476067.1	P20794-1
	MAK	ENST00000536370.6	TSL:1	c.*1688C>A		3_prime_UTR	Exon 13 of 13	ENSP00000442221.2	P20794-3

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126444 AN: 152074 Hom.: 52966 Cov.: 32

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.800

GnomAD4 exome AF: 0.843 AC: 364 AN: 432 Hom.: 151 Cov.: 0 AF XY: 0.867 AC XY: 222 AN XY: 256

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) AF: 0.841 AC: 355 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AF: 1.00 AC: 6 AN: 6

GnomAD4 genome AF: 0.832 AC: 126553 AN: 152192 Hom.: 53012 Cov.: 32 AF XY: 0.834 AC XY: 62071 AN XY: 74424

African (AFR) AF: 0.934 AC: 38767 AN: 41526

American (AMR) AF: 0.779 AC: 11905 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2478 AN: 3472

East Asian (EAS) AF: 0.920 AC: 4772 AN: 5186

South Asian (SAS) AF: 0.816 AC: 3940 AN: 4826

European-Finnish (FIN) AF: 0.870 AC: 9211 AN: 10592

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52881 AN: 67986

Other (OTH) AF: 0.797 AC: 1682 AN: 2110

Alfa AF: 0.785 Hom.: 79324

Bravo AF: 0.831

Asia WGS AF: 0.865 AC: 3005 AN: 3476

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.3
DANN	Benign	0.63
PhyloP100		1.5
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: rs501948; hg19: chr6-10762997;