10-100984457-T-C

Variant names:

• chr10-100984457-T-C
• rs2295716
• NM_017893.4:c.*326T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017893.4(SEMA4G):​c.*326T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,517,328 control chromosomes in the GnomAD database, including 46,429 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 0.28 (6658 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39771 hom.)
• Consequence: SEMA4G NM_017893.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 21 publications found

Genes affected

SEMA4G (HGNC:10735): (semaphorin 4G) Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

MRPL43 (HGNC:14517): (mitochondrial ribosomal protein L43) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. This gene and the gene for a semaphorin class 4 protein (SEMA4G) overlap at map location 10q24.31 and are transcribed in opposite directions. Sequence analysis identified multiple transcript variants encoding at least four different protein isoforms. [provided by RefSeq, Jul 2008]

ENSG00000236662 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017893.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA4G	NM_017893.4	MANE Select	c.*326T>C		3_prime_UTR	Exon 15 of 15	NP_060363.2
	SEMA4G	NM_001393925.1		c.*326T>C		3_prime_UTR	Exon 15 of 15	NP_001380854.1
	SEMA4G	NM_001203244.1		c.1706-33T>C		intron	N/A	NP_001190173.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA4G	ENST00000210633.4	TSL:1 MANE Select	c.*326T>C		3_prime_UTR	Exon 15 of 15	ENSP00000210633.3
	SEMA4G	ENST00000517724.5	TSL:1	c.1706-33T>C		intron	N/A	ENSP00000430175.1
	MRPL43	ENST00000318325.6	TSL:1	c.466-640A>G		intron	N/A	ENSP00000315364.2

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41905 AN: 151954 Hom.: 6642 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.252

GnomAD2 exomes AF: 0.282 AC: 35889 AN: 127294 AF XY: 0.276

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.369

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.554

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.229 AC: 312509 AN: 1365256 Hom.: 39771 Cov.: 63 AF XY: 0.230 AC XY: 154133 AN XY: 671192

African (AFR) AF: 0.417 AC: 12962 AN: 31106

American (AMR) AF: 0.359 AC: 12437 AN: 34644

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3298 AN: 24000

East Asian (EAS) AF: 0.553 AC: 19566 AN: 35384

South Asian (SAS) AF: 0.291 AC: 22420 AN: 76954

European-Finnish (FIN) AF: 0.182 AC: 6062 AN: 33356

Middle Eastern (MID) AF: 0.204 AC: 1019 AN: 5000

European-Non Finnish (NFE) AF: 0.207 AC: 220864 AN: 1067806

Other (OTH) AF: 0.244 AC: 13881 AN: 57006

GnomAD4 genome AF: 0.276 AC: 41960 AN: 152072 Hom.: 6658 Cov.: 32 AF XY: 0.278 AC XY: 20643 AN XY: 74336

African (AFR) AF: 0.396 AC: 16406 AN: 41468

American (AMR) AF: 0.299 AC: 4576 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3468

East Asian (EAS) AF: 0.547 AC: 2822 AN: 5156

South Asian (SAS) AF: 0.305 AC: 1469 AN: 4814

European-Finnish (FIN) AF: 0.173 AC: 1837 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13642 AN: 67974

Other (OTH) AF: 0.255 AC: 535 AN: 2102

Alfa AF: 0.221 Hom.: 5047

Bravo AF: 0.294

Asia WGS AF: 0.416 AC: 1446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.84
PhyloP100		-0.50
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2295716; hg19: chr10-102744214; COSMIC: COSV52967164; COSMIC: COSV52967164;