7-838834-G-A

Variant names:

• chr7-838834-G-A
• rs76073621
• NM_001130965.3:c.114G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001130965.3(SUN1):​c.114G>A​(p.Thr38Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00614 in 1,566,222 control chromosomes in the GnomAD database, including 543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (52 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (491 hom.)
• Consequence: SUN1 NM_001130965.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.800
• Publications: 4 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 7-838834-G-A is Benign according to our data. Variant chr7-838834-G-A is described in ClinVar as Benign. ClinVar VariationId is 461639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130965.3. 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.114G>A	p.Thr38Thr	synonymous	Exon 2 of 19	NP_001124437.1
	SUN1	NM_001367651.1		c.333G>A	p.Thr111Thr	synonymous	Exon 3 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.114G>A	p.Thr38Thr	synonymous	Exon 3 of 23	NP_001354634.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.114G>A	p.Thr38Thr	synonymous	Exon 2 of 19	ENSP00000384015.1
	SUN1	ENST00000457378.6	TSL:1	c.177G>A	p.Thr59Thr	synonymous	Exon 4 of 7	ENSP00000395952.2
	SUN1	ENST00000405266.5	TSL:5	c.114G>A	p.Thr38Thr	synonymous	Exon 2 of 20	ENSP00000384116.1

Frequencies

GnomAD3 genomes AF: 0.00759 AC: 1155 AN: 152124 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.0147 AC: 2640 AN: 180074 AF XY: 0.0141

Gnomad AFR exome AF: 0.000275

Gnomad AMR exome AF: 0.000473

Gnomad ASJ exome AF: 0.00333

Gnomad EAS exome AF: 0.150

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.00142

Gnomad OTH exome AF: 0.00670

GnomAD4 exome AF: 0.00598 AC: 8456 AN: 1413980 Hom.: 491 Cov.: 30 AF XY: 0.00604 AC XY: 4222 AN XY: 698708

African (AFR) AF: 0.000153 AC: 5 AN: 32786

American (AMR) AF: 0.000409 AC: 15 AN: 36666

Ashkenazi Jewish (ASJ) AF: 0.00294 AC: 74 AN: 25196

East Asian (EAS) AF: 0.152 AC: 5752 AN: 37828

South Asian (SAS) AF: 0.00376 AC: 301 AN: 79998

European-Finnish (FIN) AF: 0.0202 AC: 1024 AN: 50596

Middle Eastern (MID) AF: 0.00280 AC: 16 AN: 5708

European-Non Finnish (NFE) AF: 0.000723 AC: 785 AN: 1086488

Other (OTH) AF: 0.00824 AC: 484 AN: 58714

GnomAD4 genome AF: 0.00760 AC: 1157 AN: 152242 Hom.: 52 Cov.: 33 AF XY: 0.00973 AC XY: 724 AN XY: 74428

African (AFR) AF: 0.000193 AC: 8 AN: 41550

American (AMR) AF: 0.000850 AC: 13 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3468

East Asian (EAS) AF: 0.140 AC: 721 AN: 5166

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4826

European-Finnish (FIN) AF: 0.0242 AC: 257 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00163 AC: 111 AN: 68010

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00225 Hom.: 0

Bravo AF: 0.00678

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Emery-Dreifuss muscular dystrophy Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SUN1-related disorder Benign:1

Feb 28, 2019

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	3.6
DANN	Benign	0.88
PhyloP100		-0.80
PromoterAI		0.0093	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=299/1	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: rs76073621; hg19: chr7-878471; COSMIC: COSV61777726; COSMIC: COSV61777726;