rs1095

Positions:

• chr4-4863211-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002448.3(MSX1):​c.*68C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,491,052 control chromosomes in the GnomAD database, including 880 homozygotes. 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: 𝑓 0.017 (134 hom., cov: 32)
  • Exomes 𝑓: 0.012 (746 hom.)
• Consequence: MSX1 NM_002448.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392

Genes affected

MSX1 (HGNC:7391): (msh homeobox 1) This gene encodes a member of the muscle segment homeobox gene family. The encoded protein functions as a transcriptional repressor during embryogenesis through interactions with components of the core transcription complex and other homeoproteins. It may also have roles in limb-pattern formation, craniofacial development, particularly odontogenesis, and tumor growth inhibition. Mutations in this gene, which was once known as homeobox 7, have been associated with nonsyndromic cleft lip with or without cleft palate 5, Witkop syndrome, Wolf-Hirschom syndrome, and autosomoal dominant hypodontia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSX1	NM_002448.3	c.*68C>T		3_prime_UTR_variant	2/2	ENST00000382723.5	NP_002439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSX1	ENST00000382723.5	c.*68C>T		3_prime_UTR_variant	2/2	1	NM_002448.3	ENSP00000372170.4

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2581 AN: 152188 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.00388

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00473

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0122 AC: 16304 AN: 1338746 Hom.: 746 Cov.: 24 AF XY: 0.0122 AC XY: 8113 AN XY: 663844

Gnomad4 AFR exome AF: 0.00316

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.00848

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.0230

Gnomad4 FIN exome AF: 0.000381

Gnomad4 NFE exome AF: 0.00392

Gnomad4 OTH exome AF: 0.0190

GnomAD4 genome AF: 0.0170 AC: 2595 AN: 152306 Hom.: 134 Cov.: 32 AF XY: 0.0186 AC XY: 1384 AN XY: 74466

Gnomad4 AFR AF: 0.00387

Gnomad4 AMR AF: 0.0796

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.0284

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00473

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.00990 Hom.: 10

Bravo AF: 0.0236

Asia WGS AF: 0.0870 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.8
DANN	Benign	0.89

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: rs1095; hg19: chr4-4864938;