chr7-48005993-C-G

Variant names:

• chr7-48005993-C-G
• rs773133097
• NM_001030019.2:c.553G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001030019.2(SUN3):​c.553G>C​(p.Ala185Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SUN3 NM_001030019.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• Publications: 0 publications found

Genes affected

SUN3 (HGNC:22429): (Sad1 and UNC84 domain containing 3) Predicted to enable protein-membrane adaptor activity. Predicted to be involved in nuclear envelope organization. Predicted to be integral component of nuclear inner membrane. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37909275).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030019.2. 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
	SUN3	NM_001030019.2	MANE Select	c.553G>C	p.Ala185Pro	missense	Exon 6 of 10	NP_001025190.1	Q8TAQ9-1
	SUN3	NM_152782.4		c.553G>C	p.Ala185Pro	missense	Exon 7 of 11	NP_689995.3
	SUN3	NM_001284350.2		c.517G>C	p.Ala173Pro	missense	Exon 7 of 11	NP_001271279.1	Q8TAQ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN3	ENST00000297325.9	TSL:5 MANE Select	c.553G>C	p.Ala185Pro	missense	Exon 6 of 10	ENSP00000297325.4	Q8TAQ9-1
	SUN3	ENST00000395572.6	TSL:1	c.553G>C	p.Ala185Pro	missense	Exon 7 of 11	ENSP00000378939.2	Q8TAQ9-1
	SUN3	ENST00000438771.5	TSL:1	c.253G>C	p.Ala85Pro	missense	Exon 3 of 8	ENSP00000409077.1	Q8TAQ9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250664 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460792 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726734

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.0000449 AC: 2 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60364

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.17
Sift	Benign	0.45	T
Sift4G	Benign	0.27	T
Polyphen		0.91	P
Vest4		0.72
MutPred		0.56		Gain of loop (P = 0.1069)
MVP		0.28
MPC		0.12
ClinPred		0.61	D
GERP RS		5.5
PromoterAI		-0.031	Neutral
Varity_R		0.56
gMVP		0.53
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs773133097; hg19: chr7-48045590;