rs3822908

Variant names:

• chr6-97151736-T-C
• rs3822908
• NM_001350599.2:c.3482+35A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350599.2(MMS22L):​c.3482+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,533,606 control chromosomes in the GnomAD database, including 32,324 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3018 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29306 hom.)
• Consequence: MMS22L NM_001350599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.78
• Publications: 11 publications found

Genes affected

MMS22L (HGNC:21475): (MMS22 like, DNA repair protein) The protein encoded by this gene forms a complex with tonsoku-like, DNA repair protein (TONSL), and this complex recognizes and repairs DNA double-strand breaks at sites of stalled or collapsed replication forks. The encoded protein also can bind with the histone-associated protein NFKBIL2 to help regulate the chromatin state at stalled replication forks. Finally, this gene appears to be overexpressed in most lung and esophageal cancers. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMS22L	NM_001350599.2	c.3482+35A>G		intron_variant	Intron 23 of 24	ENST00000683635.1	NP_001337528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMS22L	ENST00000683635.1	c.3482+35A>G		intron_variant	Intron 23 of 24		NM_001350599.2	ENSP00000508046.1
MMS22L	ENST00000514790.1	n.176A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
MMS22L	ENST00000275053.8	c.3482+35A>G		intron_variant	Intron 23 of 24	2		ENSP00000275053.4
MMS22L	ENST00000369251.6	c.3362+35A>G		intron_variant	Intron 21 of 22	2		ENSP00000358254.2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28151 AN: 152062 Hom.: 3006 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.170

GnomAD2 exomes AF: 0.226 AC: 56328 AN: 249248 AF XY: 0.222

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.524

Gnomad FIN exome AF: 0.209

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.198 AC: 273164 AN: 1381426 Hom.: 29306 Cov.: 20 AF XY: 0.198 AC XY: 136933 AN XY: 691672

African (AFR) AF: 0.136 AC: 4332 AN: 31770

American (AMR) AF: 0.275 AC: 12166 AN: 44272

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 3962 AN: 25612

East Asian (EAS) AF: 0.477 AC: 18717 AN: 39230

South Asian (SAS) AF: 0.233 AC: 19624 AN: 84124

European-Finnish (FIN) AF: 0.211 AC: 11224 AN: 53296

Middle Eastern (MID) AF: 0.185 AC: 1039 AN: 5626

European-Non Finnish (NFE) AF: 0.183 AC: 189969 AN: 1039762

Other (OTH) AF: 0.210 AC: 12131 AN: 57734

GnomAD4 genome AF: 0.185 AC: 28178 AN: 152180 Hom.: 3018 Cov.: 32 AF XY: 0.188 AC XY: 14000 AN XY: 74378

African (AFR) AF: 0.138 AC: 5724 AN: 41504

American (AMR) AF: 0.206 AC: 3158 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3468

East Asian (EAS) AF: 0.520 AC: 2688 AN: 5174

South Asian (SAS) AF: 0.241 AC: 1161 AN: 4826

European-Finnish (FIN) AF: 0.206 AC: 2177 AN: 10588

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12181 AN: 68014

Other (OTH) AF: 0.180 AC: 380 AN: 2108

Alfa AF: 0.185 Hom.: 11555

Bravo AF: 0.190

Asia WGS AF: 0.405 AC: 1408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.038
DANN	Benign	0.70
PhyloP100		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs3822908; hg19: chr6-97599612; COSMIC: COSV51516572;