3-164979294-A-G

Variant names:

• chr3-164979294-A-G
• rs73018867
• NM_001041.4:c.*68T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001041.4(SI):​c.*68T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 922,226 control chromosomes in the GnomAD database, including 17,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (7814 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9847 hom.)
• Consequence: SI NM_001041.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.922
• Publications: 6 publications found

Genes affected

SI (HGNC:10856): (sucrase-isomaltase) This gene encodes a sucrase-isomaltase enzyme that is expressed in the intestinal brush border. The encoded protein is synthesized as a precursor protein that is cleaved by pancreatic proteases into two enzymatic subunits sucrase and isomaltase. These two subunits heterodimerize to form the sucrose-isomaltase complex. This complex is essential for the digestion of dietary carbohydrates including starch, sucrose and isomaltose. Mutations in this gene are the cause of congenital sucrase-isomaltase deficiency.[provided by RefSeq, Apr 2010]

SI Gene-Disease associations (from GenCC):

• congenital sucrase-isomaltase deficiency

  Inheritance: SD, AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-164979294-A-G is Benign according to our data. Variant chr3-164979294-A-G is described in ClinVar as Benign. ClinVar VariationId is 343998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001041.4. 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
	SI	NM_001041.4	MANE Select	c.*68T>C		3_prime_UTR	Exon 48 of 48	NP_001032.2	P14410

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SI	ENST00000264382.8	TSL:1 MANE Select	c.*68T>C		3_prime_UTR	Exon 48 of 48	ENSP00000264382.3	P14410

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37126 AN: 151440 Hom.: 7785 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0635

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.137 AC: 105394 AN: 770668 Hom.: 9847 Cov.: 10 AF XY: 0.138 AC XY: 56610 AN XY: 410454

African (AFR) AF: 0.576 AC: 11692 AN: 20284

American (AMR) AF: 0.0838 AC: 3649 AN: 43560

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2477 AN: 21762

East Asian (EAS) AF: 0.0652 AC: 2373 AN: 36378

South Asian (SAS) AF: 0.179 AC: 12997 AN: 72624

European-Finnish (FIN) AF: 0.0679 AC: 3132 AN: 46124

Middle Eastern (MID) AF: 0.154 AC: 678 AN: 4410

European-Non Finnish (NFE) AF: 0.129 AC: 62764 AN: 487892

Other (OTH) AF: 0.150 AC: 5632 AN: 37634

GnomAD4 genome AF: 0.245 AC: 37205 AN: 151558 Hom.: 7814 Cov.: 32 AF XY: 0.236 AC XY: 17475 AN XY: 74058

African (AFR) AF: 0.575 AC: 23793 AN: 41362

American (AMR) AF: 0.123 AC: 1866 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 400 AN: 3462

East Asian (EAS) AF: 0.0635 AC: 328 AN: 5166

South Asian (SAS) AF: 0.159 AC: 766 AN: 4814

European-Finnish (FIN) AF: 0.0597 AC: 632 AN: 10592

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8770 AN: 67682

Other (OTH) AF: 0.200 AC: 421 AN: 2104

Alfa AF: 0.186 Hom.: 911

Bravo AF: 0.264

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Sucrase-isomaltase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.37
PhyloP100		-0.92
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: rs73018867; hg19: chr3-164697082; COSMIC: COSV52274208;