rs199999269

Variant names:

• chr7-838955-A-G
• rs199999269
• NM_001130965.3:c.235A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001130965.3(SUN1):​c.235A>G​(p.Ser79Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,605,106 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (8 hom.)
• Consequence: SUN1 NM_001130965.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.894
• 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058339536).
• BP6: Variant 7-838955-A-G is Benign according to our data. Variant chr7-838955-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 461656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	NM_001130965.3	MANE Select	c.235A>G	p.Ser79Gly	missense	Exon 2 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367651.1		c.454A>G	p.Ser152Gly	missense	Exon 3 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.235A>G	p.Ser79Gly	missense	Exon 3 of 23	NP_001354634.1	O94901-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.235A>G	p.Ser79Gly	missense	Exon 2 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000457378.6	TSL:1	c.298A>G	p.Ser100Gly	missense	Exon 4 of 7	ENSP00000395952.2	O94901-7
	SUN1	ENST00000963118.1		c.235A>G	p.Ser79Gly	missense	Exon 3 of 24	ENSP00000633177.1

Frequencies

GnomAD3 genomes AF: 0.000664 AC: 101 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00106 AC: 247 AN: 233548 AF XY: 0.00104

Gnomad AFR exome AF: 0.000284

Gnomad AMR exome AF: 0.000278

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00223

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.00177

GnomAD4 exome AF: 0.00127 AC: 1846 AN: 1452778 Hom.: 8 Cov.: 31 AF XY: 0.00123 AC XY: 891 AN XY: 721770

African (AFR) AF: 0.0000600 AC: 2 AN: 33314

American (AMR) AF: 0.000231 AC: 10 AN: 43314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25784

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.00201 AC: 169 AN: 84150

European-Finnish (FIN) AF: 0.00251 AC: 131 AN: 52216

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5742

European-Non Finnish (NFE) AF: 0.00133 AC: 1479 AN: 1108728

Other (OTH) AF: 0.000866 AC: 52 AN: 60036

GnomAD4 genome AF: 0.000663 AC: 101 AN: 152328 Hom.: 0 Cov.: 33 AF XY: 0.000806 AC XY: 60 AN XY: 74476

African (AFR) AF: 0.000216 AC: 9 AN: 41580

American (AMR) AF: 0.000327 AC: 5 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000633 Hom.: 0

Bravo AF: 0.000623

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000494 AC: 2

ESP6500EA AF: 0.00190 AC: 16

ExAC AF: 0.00108 AC: 130

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Emery-Dreifuss muscular dystrophy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.2
DANN	Benign	0.39
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.89
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Benign	0.32	T
Sift4G	Benign	0.27	T
Polyphen		0.0040	B
Vest4		0.16
MVP		0.23
MPC		0.080
ClinPred		0.020	T
GERP RS		4.4
PromoterAI		0.0028	Neutral
gMVP		0.15
Mutation Taster		=98/2	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: rs199999269; hg19: chr7-878592; COSMIC: COSV100568902; COSMIC: COSV100568902;