15-34343662-G-C

Variant names:

• chr15-34343662-G-C
• rs73376010
• NM_001284292.2:c.-35G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001284292.2(NUTM1):​c.-35G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,533,972 control chromosomes in the GnomAD database, including 18,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1795 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16383 hom.)
• Consequence: NUTM1 NM_001284292.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.134
• Publications: 7 publications found

Genes affected

NUTM1 (HGNC:29919): (NUT midline carcinoma family member 1) Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044864714).
• BP6: Variant 15-34343662-G-C is Benign according to our data. Variant chr15-34343662-G-C is described in ClinVar as Benign. ClinVar VariationId is 403246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM1	NM_001284292.2	c.-35G>C		5_prime_UTR_variant	Exon 1 of 8	ENST00000537011.6	NP_001271221.2
NUTM1	NM_001284293.2	c.30G>C	p.Lys10Asn	missense_variant	Exon 1 of 7		NP_001271222.2
NUTM1	NM_175741.3	c.-204G>C		5_prime_UTR_variant	Exon 1 of 8		NP_786883.2
NUTM1	XM_047432341.1	c.-207G>C		5_prime_UTR_variant	Exon 1 of 8		XP_047288297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM1	ENST00000537011.6	c.-35G>C		5_prime_UTR_variant	Exon 1 of 8	2	NM_001284292.2	ENSP00000444896.1
NUTM1	ENST00000333756.5	c.-204G>C		5_prime_UTR_variant	Exon 1 of 8	1		ENSP00000329448.4
NUTM1	ENST00000438749.7	c.30G>C	p.Lys10Asn	missense_variant	Exon 1 of 7	2		ENSP00000407031.3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22775 AN: 152102 Hom.: 1793 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.148

GnomAD2 exomes AF: 0.168 AC: 21590 AN: 128342 AF XY: 0.170

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.319

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.149 AC: 206075 AN: 1381752 Hom.: 16383 Cov.: 29 AF XY: 0.151 AC XY: 102664 AN XY: 681866

African (AFR) AF: 0.150 AC: 4732 AN: 31544

American (AMR) AF: 0.161 AC: 5737 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3198 AN: 25162

East Asian (EAS) AF: 0.302 AC: 10802 AN: 35722

South Asian (SAS) AF: 0.202 AC: 15968 AN: 79194

European-Finnish (FIN) AF: 0.115 AC: 3854 AN: 33444

Middle Eastern (MID) AF: 0.139 AC: 792 AN: 5688

European-Non Finnish (NFE) AF: 0.141 AC: 152448 AN: 1077462

Other (OTH) AF: 0.148 AC: 8544 AN: 57850

GnomAD4 genome AF: 0.150 AC: 22788 AN: 152220 Hom.: 1795 Cov.: 32 AF XY: 0.153 AC XY: 11424 AN XY: 74434

African (AFR) AF: 0.144 AC: 5979 AN: 41536

American (AMR) AF: 0.162 AC: 2475 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3472

East Asian (EAS) AF: 0.329 AC: 1705 AN: 5176

South Asian (SAS) AF: 0.203 AC: 978 AN: 4818

European-Finnish (FIN) AF: 0.104 AC: 1105 AN: 10592

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9566 AN: 68006

Other (OTH) AF: 0.148 AC: 312 AN: 2114

Alfa AF: 0.139 Hom.: 267

Bravo AF: 0.154

TwinsUK AF: 0.135 AC: 502

ALSPAC AF: 0.148 AC: 572

ExAC AF: 0.157 AC: 2147

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.7
DANN	Benign	0.50
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.91	T
PhyloP100		-0.13
PROVEAN	Benign	0.090	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Benign	0.71	T
Vest4		0.065
MutPred		0.15		Loss of MoRF binding (P = 0.0167);
ClinPred		0.0035	T
GERP RS		2.1
PromoterAI		0.0012	Neutral
Mutation Taster		=300/0	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: rs73376010; hg19: chr15-34635863; COSMIC: COSV107328919; COSMIC: COSV107328919;