rs78842948

chr7-841957-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001130965.3(SUN1):c.278A>C(p.Gln93Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0028 in 1,614,168 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (57 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (47 hom.)
• Consequence: SUN1 NM_001130965.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.45

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038112998).
• BP6: Variant 7-841957-A-C is Benign according to our data. Variant chr7-841957-A-C is described in ClinVar as [Benign]. Clinvar id is 461658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2133/152340) while in subpopulation AFR AF= 0.0482 (2002/41574). AF 95% confidence interval is 0.0464. There are 57 homozygotes in gnomad4. There are 1029 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 57 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN1	NM_001130965.3	c.278A>C	p.Gln93Pro	missense_variant	3/19	ENST00000401592.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN1	ENST00000401592.6	c.278A>C	p.Gln93Pro	missense_variant	3/19	1	NM_001130965.3	P3

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2130 AN: 152222 Hom.: 57 Cov.: 33

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00350 AC: 874 AN: 249398 Hom.: 15 AF XY: 0.00253 AC XY: 343 AN XY: 135348

Gnomad AFR exome AF: 0.0490

Gnomad AMR exome AF: 0.00241

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00163 AC: 2387 AN: 1461828 Hom.: 47 Cov.: 30 AF XY: 0.00141 AC XY: 1026 AN XY: 727208

Gnomad4 AFR exome AF: 0.0511

Gnomad4 AMR exome AF: 0.00268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000269

Gnomad4 OTH exome AF: 0.00369

GnomAD4 genome AF: 0.0140 AC: 2133 AN: 152340 Hom.: 57 Cov.: 33 AF XY: 0.0138 AC XY: 1029 AN XY: 74496

Gnomad4 AFR AF: 0.0482

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00253 Hom.: 13

Bravo AF: 0.0164

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0371 AC: 145

ESP6500EA AF: 0.000241 AC: 2

ExAC AF: 0.00421 AC: 509

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Emery-Dreifuss muscular dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

SUN1-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 02, 2019

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
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	23
Dann	Uncertain	0.99
Eigen	Benign	0.18
Eigen_PC	Benign	0.081
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D;.;T;T;T;D;D;D;D;D;D;D
MetaRNN	Benign	0.0038	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.90	D;D;D;D;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0070	D;D;T;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0070	D;T;T;D;D;D;D;T;T;D;T;D
Polyphen		1.0	.;D;.;.;.;.;.;.;.;.;D;.
Vest4		0.57
MVP		0.33
MPC		0.51
ClinPred		0.060	T
GERP RS		4.5
gMVP		0.18

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: rs78842948; hg19: chr7-881594;