7-84999673-T-G

Variant names:

• chr7-84999673-T-G
• rs7800072
• NM_001384900.1:c.2101A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001384900.1(SEMA3D):​c.2101A>C​(p.Lys701Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,613,526 control chromosomes in the GnomAD database, including 81,188 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.32 (7942 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73246 hom.)
• Consequence: SEMA3D NM_001384900.1 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.55

Genes affected

SEMA3D (HGNC:10726): (semaphorin 3D) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003791988).
• BP6: Variant 7-84999673-T-G is Benign according to our data. Variant chr7-84999673-T-G is described in ClinVar as [Benign]. Clinvar id is 3060976.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3D	NM_001384900.1	c.2101A>C	p.Lys701Gln	missense_variant	Exon 19 of 19	ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3D	ENST00000284136.11	c.2101A>C	p.Lys701Gln	missense_variant	Exon 19 of 19	5	NM_001384900.1	ENSP00000284136.6
SEMA3D	ENST00000484038.1	n.1227A>C		non_coding_transcript_exon_variant	Exon 10 of 10	1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48715 AN: 151768 Hom.: 7934 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.325

GnomAD2 exomes AF: 0.281 AC: 70729 AN: 251380 AF XY: 0.283

Gnomad AFR exome AF: 0.372

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.278

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.313 AC: 457173 AN: 1461642 Hom.: 73246 Cov.: 36 AF XY: 0.310 AC XY: 225403 AN XY: 727138

Gnomad4 AFR exome AF: 0.370 AC: 12393 AN: 33478

Gnomad4 AMR exome AF: 0.187 AC: 8355 AN: 44700

Gnomad4 ASJ exome AF: 0.287 AC: 7512 AN: 26134

Gnomad4 EAS exome AF: 0.238 AC: 9459 AN: 39696

Gnomad4 SAS exome AF: 0.208 AC: 17967 AN: 86258

Gnomad4 FIN exome AF: 0.247 AC: 13202 AN: 53410

Gnomad4 NFE exome AF: 0.331 AC: 367988 AN: 1111816

Gnomad4 Remaining exome AF: 0.306 AC: 18495 AN: 60382

GnomAD4 genome AF: 0.321 AC: 48743 AN: 151884 Hom.: 7942 Cov.: 32 AF XY: 0.315 AC XY: 23356 AN XY: 74212

Gnomad4 AFR AF: 0.375 AC: 0.374577 AN: 0.374577

Gnomad4 AMR AF: 0.261 AC: 0.260639 AN: 0.260639

Gnomad4 ASJ AF: 0.297 AC: 0.296659 AN: 0.296659

Gnomad4 EAS AF: 0.283 AC: 0.282541 AN: 0.282541

Gnomad4 SAS AF: 0.199 AC: 0.199168 AN: 0.199168

Gnomad4 FIN AF: 0.240 AC: 0.240125 AN: 0.240125

Gnomad4 NFE AF: 0.327 AC: 0.326591 AN: 0.326591

Gnomad4 OTH AF: 0.323 AC: 0.323362 AN: 0.323362

Alfa AF: 0.324 Hom.: 23541

Bravo AF: 0.324

TwinsUK AF: 0.315 AC: 1169

ALSPAC AF: 0.329 AC: 1268

ESP6500AA AF: 0.373 AC: 1642

ESP6500EA AF: 0.327 AC: 2814

ExAC AF: 0.287 AC: 34869

Asia WGS AF: 0.223 AC: 776 AN: 3478

EpiCase AF: 0.332

EpiControl AF: 0.325

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SEMA3D-related disorder Benign:1

Jul 19, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	16
DANN	Benign	0.67
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.10
Sift	Benign	0.66	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.015
MPC		0.16
ClinPred		0.0016	T
GERP RS		3.8
Varity_R		0.092
gMVP		0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs7800072; hg19: chr7-84628989; COSMIC: COSV52394115;