5-179765340-A-G

Position:

• chr5-179765340-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014757.5(MAML1):​c.330A>G​(p.Thr110Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 1,596,726 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (50 hom.)
• Consequence: MAML1 NM_014757.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

Genes affected

MAML1 (HGNC:13632): (mastermind like transcriptional coactivator 1) This protein is the human homolog of mastermind, a Drosophila protein that plays a role in the Notch signaling pathway involved in cell-fate determination. There is in vitro evidence that the human homolog forms a complex with the intracellular portion of human Notch receptors and can increase expression of a Notch-induced gene. This evidence supports its proposed function as a transcriptional co-activator in the Notch signaling pathway. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 5-179765340-A-G is Benign according to our data. Variant chr5-179765340-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.36 with no splicing effect.
• BS2: High AC in GnomAd4 at 731 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAML1	NM_014757.5	c.330A>G	p.Thr110Thr	synonymous_variant	2/5	ENST00000292599.4	NP_055572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAML1	ENST00000292599.4	c.330A>G	p.Thr110Thr	synonymous_variant	2/5	1	NM_014757.5	ENSP00000292599.3

Frequencies

GnomAD3 genomes AF: 0.00480 AC: 731 AN: 152232 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00869

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00426 AC: 1011 AN: 237142 Hom.: 5 AF XY: 0.00433 AC XY: 556 AN XY: 128382

Gnomad AFR exome AF: 0.00181

Gnomad AMR exome AF: 0.00166

Gnomad ASJ exome AF: 0.00206

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000956

Gnomad FIN exome AF: 0.00133

Gnomad NFE exome AF: 0.00762

Gnomad OTH exome AF: 0.00507

GnomAD4 exome AF: 0.00734 AC: 10604 AN: 1444376 Hom.: 50 Cov.: 31 AF XY: 0.00703 AC XY: 5050 AN XY: 718180

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.00184

Gnomad4 ASJ exome AF: 0.00261

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000728

Gnomad4 FIN exome AF: 0.00190

Gnomad4 NFE exome AF: 0.00897

Gnomad4 OTH exome AF: 0.00581

GnomAD4 genome AF: 0.00480 AC: 731 AN: 152350 Hom.: 2 Cov.: 32 AF XY: 0.00436 AC XY: 325 AN XY: 74498

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00169

Gnomad4 NFE AF: 0.00869

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00625 Hom.: 2

Bravo AF: 0.00447

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

MAML1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.44
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs146593514; hg19: chr5-179192341;