15-89751050-A-G

Variant names:

• chr15-89751050-A-G
• NM_018670.4:c.182T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018670.4(MESP1):​c.182T>C​(p.Leu61Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000085 in 1,176,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L61R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: MESP1 NM_018670.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061225325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP1	NM_018670.4	c.182T>C	p.Leu61Pro	missense_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.182T>C	p.Leu61Pro	missense_variant	Exon 1 of 2	1	NM_018670.4	ENSP00000300057.4
MESP1	ENST00000559894.1	n.88T>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.50e-7 AC: 1 AN: 1176066 Hom.: 0 Cov.: 56 AF XY: 0.00000176 AC XY: 1 AN XY: 568190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.9
DANN	Benign	0.61
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.14	T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.089
Sift	Benign	0.31	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.037
MutPred		0.25		Gain of relative solvent accessibility (P = 0.0249);
MVP		0.12
MPC		0.72
ClinPred		0.076	T
GERP RS		-1.6
Varity_R		0.047
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-90294281;