chr5-179765400-C-T

Variant names:

• chr5-179765400-C-T
• rs113715124
• NM_014757.5:c.390C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014757.5(MAML1):​c.390C>T​(p.Tyr130Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00714 in 1,614,054 control chromosomes in the GnomAD database, including 54 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: 0.0074 (52 hom.)
• Consequence: MAML1 NM_014757.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 5-179765400-C-T is Benign according to our data. Variant chr5-179765400-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.35 with no splicing effect.
• BS2: High AC in GnomAd4 at 738 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014757.5. 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
	MAML1	NM_014757.5	MANE Select	c.390C>T	p.Tyr130Tyr	synonymous	Exon 2 of 5	NP_055572.1	Q92585

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAML1	ENST00000292599.4	TSL:1 MANE Select	c.390C>T	p.Tyr130Tyr	synonymous	Exon 2 of 5	ENSP00000292599.3	Q92585
	MAML1	ENST00000933871.1		c.390C>T	p.Tyr130Tyr	synonymous	Exon 2 of 5	ENSP00000603930.1

Frequencies

GnomAD3 genomes AF: 0.00485 AC: 738 AN: 152166 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00870

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00421 AC: 1057 AN: 251272 AF XY: 0.00434

Gnomad AFR exome AF: 0.00179

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.00761

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00738 AC: 10782 AN: 1461770 Hom.: 52 Cov.: 31 AF XY: 0.00706 AC XY: 5135 AN XY: 727196

African (AFR) AF: 0.00119 AC: 40 AN: 33476

American (AMR) AF: 0.00181 AC: 81 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 68 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000719 AC: 62 AN: 86244

European-Finnish (FIN) AF: 0.00189 AC: 101 AN: 53416

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00906 AC: 10074 AN: 1111936

Other (OTH) AF: 0.00583 AC: 352 AN: 60394

GnomAD4 genome AF: 0.00485 AC: 738 AN: 152284 Hom.: 2 Cov.: 32 AF XY: 0.00443 AC XY: 330 AN XY: 74458

African (AFR) AF: 0.00183 AC: 76 AN: 41554

American (AMR) AF: 0.00255 AC: 39 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00870 AC: 592 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00671 Hom.: 2

Bravo AF: 0.00451

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00834

EpiControl AF: 0.00705

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.14
DANN	Benign	0.88
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs113715124; hg19: chr5-179192401; COSMIC: COSV52982749; COSMIC: COSV52982749;