rs4276595

Variant names:

• chr7-142065905-T-C
• rs4276595
• NM_001365693.1:c.4770+74T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365693.1(MGAM):​c.4770+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 1,180,072 control chromosomes in the GnomAD database, including 5,618 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.080 (1527 hom., cov: 28)
  • Exomes 𝑓: 0.037 (4091 hom.)
• Consequence: MGAM NM_001365693.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

Genes affected

MGAM (HGNC:7043): (maltase-glucoamylase) This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAM	NM_001365693.1	c.4770+74T>C		intron_variant	Intron 40 of 70	ENST00000475668.6	NP_001352622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAM	ENST00000475668.6	c.4770+74T>C		intron_variant	Intron 40 of 70	5	NM_001365693.1	ENSP00000417515.2
MGAM	ENST00000549489.6	c.4618+437T>C		intron_variant	Intron 38 of 47	1		ENSP00000447378.2
MGAM	ENST00000620571.1	c.4770+74T>C		intron_variant	Intron 40 of 47	5		ENSP00000482292.1

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 11567 AN: 144492 Hom.: 1517 Cov.: 28

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00708

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.000608

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0822

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0774

GnomAD4 exome AF: 0.0367 AC: 38052 AN: 1035464 Hom.: 4091 AF XY: 0.0365 AC XY: 18955 AN XY: 519014

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.0287

Gnomad4 ASJ exome AF: 0.0415

Gnomad4 EAS exome AF: 0.000222

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.0324

Gnomad4 OTH exome AF: 0.0466

GnomAD4 genome AF: 0.0803 AC: 11618 AN: 144608 Hom.: 1527 Cov.: 28 AF XY: 0.0777 AC XY: 5473 AN XY: 70418

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0422

Gnomad4 ASJ AF: 0.0424

Gnomad4 EAS AF: 0.000610

Gnomad4 SAS AF: 0.0419

Gnomad4 FIN AF: 0.0209

Gnomad4 NFE AF: 0.0356

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0593 Hom.: 189

Asia WGS AF: 0.0320 AC: 110 AN: 3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs4276595; hg19: chr7-141765705;