rs7800072

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• 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
• Publications: 37 publications found

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]

SEMA3D Gene-Disease associations (from GenCC):

• skeletal dysplasia

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384900.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	NM_001384900.1	MANE Select	c.2101A>C	p.Lys701Gln	missense	Exon 19 of 19	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.2101A>C	p.Lys701Gln	missense	Exon 20 of 20	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.2101A>C	p.Lys701Gln	missense	Exon 21 of 21	NP_001371831.1	O95025

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	ENST00000284136.11	TSL:5 MANE Select	c.2101A>C	p.Lys701Gln	missense	Exon 19 of 19	ENSP00000284136.6	O95025
	SEMA3D	ENST00000484038.1	TSL:1	n.1227A>C		non_coding_transcript_exon	Exon 10 of 10
	SEMA3D	ENST00000916323.1		c.2101A>C	p.Lys701Gln	missense	Exon 18 of 18	ENSP00000586382.1

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

African (AFR) AF: 0.370 AC: 12393 AN: 33478

American (AMR) AF: 0.187 AC: 8355 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7512 AN: 26134

East Asian (EAS) AF: 0.238 AC: 9459 AN: 39696

South Asian (SAS) AF: 0.208 AC: 17967 AN: 86258

European-Finnish (FIN) AF: 0.247 AC: 13202 AN: 53410

Middle Eastern (MID) AF: 0.312 AC: 1802 AN: 5768

European-Non Finnish (NFE) AF: 0.331 AC: 367988 AN: 1111816

Other (OTH) 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

African (AFR) AF: 0.375 AC: 15500 AN: 41380

American (AMR) AF: 0.261 AC: 3981 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3472

East Asian (EAS) AF: 0.283 AC: 1450 AN: 5132

South Asian (SAS) AF: 0.199 AC: 958 AN: 4810

European-Finnish (FIN) AF: 0.240 AC: 2541 AN: 10582

Middle Eastern (MID) AF: 0.321 AC: 93 AN: 290

European-Non Finnish (NFE) AF: 0.327 AC: 22184 AN: 67926

Other (OTH) AF: 0.323 AC: 681 AN: 2106

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

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEMA3D-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.6
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

Other links and lift over

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