rs2305440

Variant names:

• chr15-89750563-G-A
• rs2305440
• NM_018670.4:c.669C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-89750563-G-A
• chr15-89750563-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018670.4(MESP1):​c.669C>T​(p.Phe223Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000761 in 1,314,312 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 35)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: MESP1 NM_018670.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 14 publications found

Genes affected

MESP1 (HGNC:29658): (mesoderm posterior bHLH transcription factor 1) Enables DNA-binding transcription factor activity and transcription cis-regulatory region binding activity. Involved in several processes, including endothelial cell differentiation; heart development; and positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.256 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP1	NM_018670.4	c.669C>T	p.Phe223Phe	synonymous_variant	Exon 1 of 2	ENST00000300057.5	NP_061140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MESP1	ENST00000300057.5	c.669C>T	p.Phe223Phe	synonymous_variant	Exon 1 of 2	1	NM_018670.4	ENSP00000300057.4
MESP1	ENST00000559894.1	n.115-336C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD2 exomes AF: 0.00 AC: 0 AN: 78758 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.61e-7 AC: 1 AN: 1314312 Hom.: 0 Cov.: 59 AF XY: 0.00 AC XY: 0 AN XY: 644016

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27854

American (AMR) AF: 0.00 AC: 0 AN: 26544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19960

East Asian (EAS) AF: 0.00 AC: 0 AN: 34172

South Asian (SAS) AF: 0.00 AC: 0 AN: 67640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4562

European-Non Finnish (NFE) AF: 9.54e-7 AC: 1 AN: 1047836

Other (OTH) AF: 0.00 AC: 0 AN: 54292

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.3
DANN	Benign	0.76
PhyloP100		0.26

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: rs2305440; hg19: chr15-90293794;