7-838946-G-T

Variant names:

• chr7-838946-G-T
• rs114826023
• NM_001130965.3:c.226G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001367635.1(SUN1):​c.-232G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,607,632 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: SUN1 NM_001367635.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.117
• Publications: 2 publications found

Genes affected

SUN1 (HGNC:18587): (Sad1 and UNC84 domain containing 1) This gene is a member of the unc-84 homolog family and encodes a nuclear envelope protein with an Unc84 (SUN) domain. The protein is involved in nuclear anchorage and migration. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2019]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029521585).
• BP6: Variant 7-838946-G-T is Benign according to our data. Variant chr7-838946-G-T is described in ClinVar as Benign. ClinVar VariationId is 461655.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367635.1. 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
	SUN1	NM_001130965.3	MANE Select	c.226G>T	p.Gly76Cys	missense	Exon 2 of 19	NP_001124437.1
	SUN1	NM_001367635.1		c.-232G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 21	NP_001354564.1
	SUN1	NM_001367658.1		c.-536G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 20	NP_001354587.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.226G>T	p.Gly76Cys	missense	Exon 2 of 19	ENSP00000384015.1
	SUN1	ENST00000457378.6	TSL:1	c.289G>T	p.Gly97Cys	missense	Exon 4 of 7	ENSP00000395952.2
	SUN1	ENST00000963118.1		c.226G>T	p.Gly76Cys	missense	Exon 3 of 24	ENSP00000633177.1

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 243 AN: 152182 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000350 AC: 83 AN: 237356 AF XY: 0.000333

Gnomad AFR exome AF: 0.00546

Gnomad AMR exome AF: 0.0000610

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000574

Gnomad FIN exome AF: 0.0000489

Gnomad NFE exome AF: 0.00000921

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000152 AC: 221 AN: 1455332 Hom.: 1 Cov.: 31 AF XY: 0.000153 AC XY: 111 AN XY: 723382

African (AFR) AF: 0.00563 AC: 188 AN: 33390

American (AMR) AF: 0.000160 AC: 7 AN: 43852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39530

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52488

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5752

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109792

Other (OTH) AF: 0.000366 AC: 22 AN: 60168

GnomAD4 genome AF: 0.00160 AC: 244 AN: 152300 Hom.: 0 Cov.: 33 AF XY: 0.00156 AC XY: 116 AN XY: 74482

African (AFR) AF: 0.00560 AC: 233 AN: 41580

American (AMR) AF: 0.000392 AC: 6 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000450 Hom.: 0

Bravo AF: 0.00168

ESP6500AA AF: 0.00395 AC: 16

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000422 AC: 51

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Emery-Dreifuss muscular dystrophy (1)
-	-	1	SUN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.80
DANN	Benign	0.52
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.12
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.076
Sift	Benign	0.24	T
Sift4G	Benign	0.26	T
Polyphen		0.0040	B
Vest4		0.095
MVP		0.093
MPC		0.091
ClinPred		0.0011	T
GERP RS		-2.4
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.16
Mutation Taster		=94/6	polymorphism

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: rs114826023; hg19: chr7-878583;